Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
권호 표지
DOI QR코드

DOI QR Code

Anti-Proliferation Effects and Molecular Mechanisms of Action of Tetramethypyrazine on Human SGC-7901 Gastric Carcinoma Cells

  • Ji, Ai-Jun (First Clinical Medical College, Nanjing University of Chinese Medicine) ;
  • Liu, Sheng-Lin (Department of Oncology, Jiangsu Provincial Hospital of Traditional Chinese Medicine) ;
  • Ju, Wen-Zheng (Clinical Pharmacology Laboratory, Jiangsu Provincial Hospital of Traditional Chinese Medicine) ;
  • Huang, Xin-En (Department of Chemotherapy, the Affiliated Jiangsu Cancer Hospital of Nanjing Medical University & Jiangsu Institute of Cancer Research)
  • Published : 2014.04.30
Download PDF
⟨ Previous Next ⟩

Abstract

Aim: To investigate the effects of tetramethypyrazine (TMP) on proliferation and apoptosis of the human gastric carcinoma cell line 7901 and its possible mechanism of action. Methods: The viability of TMP-treated 7901 cells was measured with a 3-(4, 5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide assay (MTT) and cell apoptosis was analyzed by flow cytometry. The distribution of cells in different phases of cell cycle after exposure of TMPs was analyzed with flow cytometry. To investigate the molecular mechanisms of TMP-mediated apoptosis, the expression of NF-${\kappa}Bp65$, cyclinD1 and p16 in SGC-7901 cells was analyzed by reverse transcription-polymerase chain reaction (RT-PCR) and western blotting. Results: TMP inhibited the proliferation of human gastric carcinoma cell line 7901 in dose and time dependent manners. Cell growth was suppressed by TMP at different concentrations (0.25, 0.5, 1.0, 2.0 mg/ml), the inhibition rate is 0.46%, 4.36%, 14.8%, 76.1% (48h) and 15.5%, 18.5%, 41.2%, 89.8% (72h) respectively. When the concentration of TMPs was 2.0mg/ml, G1-phase arrest in the SGC-7901 cells was significant based on the data for cell cycle distribution. RT-PCR demonstrated that NF-${\kappa}Bp65$ and cyclin D1 mRNA expression was significantly down-regulated in 7901 cells treated with 2.0 mg/ml TMP for 72h (p<0.05), while the p16 mRNA level was up-regulated (p<0.05). The protein expression of NF-${\kappa}Bp65$ and cyclin D1 decreased gradually with the increase in TMP concentration, compared with control cells (p<0.05), while expression of protein p16 was up-regulated (p<0.01). Conclusion: TMP exhibits significant anti-proliferative and pro-apoptotic effects on the human gastric carcinoma cell line SGC-7901. NF-${\kappa}Bp65$, cyclinD1 and p16 may also play important roles in the regulation mechanisms.

Keywords

References

  1. Basiri Z, Safaralizadeh R, Bonyadi MJ, et al (2014). Helicobacter pylori vacA d1 genotype predicts risk of gastric adenocarcinoma and peptic ulcers in northwestern Iran. Asian Pac J Cancer Prev, 15, 1575-9. https://doi.org/10.7314/APJCP.2014.15.4.1575
  2. Behnampour N, Hajizadeh E, Zayeri F, et al (2014). Modeling of influential predictors of gastric cancer incidence rates in golestan province, north iran. Asian Pac J Cancer Prev, 15, 1111-7. https://doi.org/10.7314/APJCP.2014.15.3.1111
  3. Calik M, Calik I, Demirci E, et al (2014). Goseki grade and tumour location influence survival of patients with gastric cancer. Asian Pac J Cancer Prev, 15, 1429-34. https://doi.org/10.7314/APJCP.2014.15.3.1429
  4. Cao J, Huang XE, Liu J, et al (2013). Comparison of efficacy and toxicity of first line chemotherapy with or without epirubicin for patients with advanced stage soft tissue sarcoma. Asian Pac J Cancer Prev, 14, 7171-7. https://doi.org/10.7314/APJCP.2013.14.12.7171
  5. Chen G, Shen ZL, Wang L, et al (2013). Hsa-miR-181a-5p expression and effects on cell proliferation in gastric cancer. Asian Pac J Cancer Prev, 14, 3871-5. https://doi.org/10.7314/APJCP.2013.14.6.3871
  6. Chen YS, Xu SX, Ding YB, et al (2013). Helicobacter pylori Infection and the risk of colorectal adenoma and adenocarcinoma: an updated meta-analysis of different testing methods. Asian Pac J Cancer Prev, 14, 7613-9. https://doi.org/10.7314/APJCP.2013.14.12.7613
  7. Chen YS, Xu SX, Ding YB, et al (2013). Colorectal cancer screening in high-risk populations: a survey of cognition among medical professionals in Jiangsu, China. Asian Pac J Cancer Prev, 14, 6487-91. https://doi.org/10.7314/APJCP.2013.14.11.6487
  8. Dai XZ, Yin HT, Sun LF, et al (2013). Potential therapeutic efficacy of curcumin in liver cancer. Asian Pac J Cancer Prev, 14, 3855-9. https://doi.org/10.7314/APJCP.2013.14.6.3855
  9. Deng QQ, Huang XE, Ye LH, et al (2013). Phase II trial of Loubo(R) (Lobaplatin) and pemetrexed for patients with metastatic breast cancer not responding to anthracycline or taxanes. Asian Pac J Cancer Prev, 14, 413-7. https://doi.org/10.7314/APJCP.2013.14.1.413
  10. Cui L, Liu XX, Jiang Y, et al (2014). Phase II study on dose escalating schedule of paclitaxel concurrent with radiotherapy in treating patients with locally advanced non-small cell lung cancer. Asian Pac J Cancer Prev, 15, 1699-702. https://doi.org/10.7314/APJCP.2014.15.4.1699
  11. Deng W, Long L, Li JL, et al (2014). Mortality of major cancers in guangxi, china: sex, age and geographical differences from 1971 and 2005. Asian Pac J Cancer Prev, 15, 1567-74. https://doi.org/10.7314/APJCP.2014.15.4.1567
  12. Ferlay J, Shin HR, Bray F, et al (2010). Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer, 127, 2893-917. https://doi.org/10.1002/ijc.25516
  13. Fei ZH, Yao CY, Yang XL, Huang XE, Ma SL (2013). Serum BMP-2 up-regulation as an indicator of poor survival in advanced non-small cell lung cancer patients. Asian Pac J Cancer Prev, 14, 5293-9. https://doi.org/10.7314/APJCP.2013.14.9.5293
  14. Hernandez BY, Green MD, Cassel KD, et al (2010). review of Hawaii Cancer Facts and Figure s 2010. Hawaii Med J, 69, 223-24.
  15. Hinz M, Krappmann D, Eichten A, et al (1999). NF-kappa B function in growth control: regulation of cyclinD1 expression and G0/G1-to-S-Phase transition. Mol Cell Biol, 19, 2690-98.
  16. Hou ZB, Lu KJ, Wu XL, et al (2014). In vitro and in vivo antitumor evaluation of berbamine for lung cancer treatment. Asian Pac J Cancer Prev, 15, 1767-9. https://doi.org/10.7314/APJCP.2014.15.4.1767
  17. Gong JP, Yang L, Huang XE, et al (2014). Outcomes based on risk assessment of anastomotic leakage after rectal cancer surgery. Asian Pac J Cancer Prev, 15, 707-12. https://doi.org/10.7314/APJCP.2014.15.2.707
  18. Gu M, Li SY, Huang XE, et al (2013). A phase II study on continuous infusional paclitaxel and 5-Fu as first-line chemotherapy for patients with advanced esophageal cancer. Asian Pac J Cancer Prev, 13, 5587-91. https://doi.org/10.7314/APJCP.2012.13.11.5587
  19. Huang XE, Wei GL, Huo JG, et al (2013). Intrapleural or intraperitoneal lobaplatin for treatment of patients with malignant pleural effusion or ascites. Asian Pac J Cancer Prev, 14, 2611-4. https://doi.org/10.7314/APJCP.2013.14.4.2611
  20. Huang XE, Tian GY, Cao J, et al (2013). Pemetrexed as a component of first-, second- and third- line chemotherapy in treating patients with metastatic lung adenocarcinoma. Asian Pac J Cancer Prev, 14, 6663-7. https://doi.org/10.7314/APJCP.2013.14.11.6663
  21. Kishimoto I, Mitomi H, Ohkura Y, et al (2008). Abnormal expression of p16 (INK4a), D1, cyclin-dependent kinase 4 and retinoblastoma protein in gastric carcinomas. J Surg Oncol. 98, 60-6. https://doi.org/10.1002/jso.21087
  22. Khoshbaten M, Pishahang P, Nouri M, et al (2014). Diagnostic value of fecal calprotectin as a screening biomarker for gastrointestinal malignancies. Asian Pac J Cancer Prev, 15, 1667-70. https://doi.org/10.7314/APJCP.2014.15.4.1667
  23. Karim S (2014). Clinicopathological and p53 gene alteration comparison between young and older patients with gastric cancer. Asian Pac J Cancer Prev, 15, 1375-9. https://doi.org/10.7314/APJCP.2014.15.3.1375
  24. Liu E, Li X, Yan F, et al (2004). Cyclin-dependent kinases phosphorylate human Cdt1 and induce its degradation. J Biol Chem, 279, 17283-88. https://doi.org/10.1074/jbc.C300549200
  25. Liu YC, Zhou SB, Gao F, et al (2013). Phase II study on breast conservative surgery plus chemo- and radiotherapy in treating Chinese patients with early staged breast cancer. Asian Pac J Cancer Prev, 14, 3747-50. https://doi.org/10.7314/APJCP.2013.14.6.3747
  26. Liu YC, Zhou SB, Gao F, et al (2013). Chemotherapy and late course three dimensional conformal radiotherapy for treatment of patients with stage III non- small cell lung cancer. Asian Pac J Cancer Prev, 14, 2663-5. https://doi.org/10.7314/APJCP.2013.14.4.2663
  27. Liu J, Huang XE, Tian GY, et al (2013). Phase II study on safety and efficacy of Yadanzi(R) (Javanica oil emulsion injection) combined with chemotherapy for patients with gastric cancer. Asian Pac J Cancer Prev, 14, 2009-12. https://doi.org/10.7314/APJCP.2013.14.3.2009
  28. Lu YF, Liu ZC, Li ZH, et al (2014). Esophageal/gastric cancer screening in high-risk populations in Henan Province, China. Asian Pac J Cancer Prev, 15, 1419-22. https://doi.org/10.7314/APJCP.2014.15.3.1419
  29. Lu YY, Huang XE, Cao J, et al (2013). Phase II study on javanica oil emulsion injection (Yadanzi(R)) combined with chemotherapy in treating patients with advanced lung adenocarcinoma. Asian Pac J Cancer Prev, 14, 4791-4. https://doi.org/10.7314/APJCP.2013.14.8.4791
  30. Lu YY, Huang XE, Xu L, et al (2013). Potential predictors of sensitivity to pemetrexed as first-line chemotherapy for patients with advanced non-squamous NSCLCs. Asian Pac J Cancer Prev, 14, 2005-8. https://doi.org/10.7314/APJCP.2013.14.3.2005
  31. Murray AW, Marks D (2001). Can sequencing shed light on cell cycling. Nature, 409, 844-6. https://doi.org/10.1038/35057033
  32. Parkin DM, Bray F, Ferlay J, Pisani P (2005). Global cancer statistics, 2002. CA ancer J Clin, 55, 74-108. https://doi.org/10.3322/canjclin.55.2.74
  33. Pestell K (2004). Cell cycle independent activity of cyclin D1. Drug Discov Today, 8, 911-2
  34. Shanmugam Sambantham, Mahendran Radha, Arumugam Paramasivam, etal (2013). Molecular Mechanism Underlying Hesperetin-induced Apoptosis by in silico Analysis and in Prostate Cancer PC-3 cells. Asian Pac J Cancer Prev, 14, 4347-52. https://doi.org/10.7314/APJCP.2013.14.7.4347
  35. Shen B, Zheng MQ, Lu JW, et al (2013). CXCL12-CXCR4 promotes proliferation and invasion of pancreatic cancer cells. Asian Pac J Cancer Prev, 14, 5403-8. https://doi.org/10.7314/APJCP.2013.14.9.5403
  36. Sun MQ, Meng AF, Huang XE, et al (2013). Comparison of psychological influence on breast cancer patients between breast-conserving surgery and modified radical mastectomy. Asian Pac J Cancer Prev, 14, 149-52. https://doi.org/10.7314/APJCP.2013.14.1.149
  37. Umit Zeybek, Ilhan Yaylım, Nazli Ezgi Ozkan, et al (2013). Cyclin D1 Gene G870A Variants and Primary Brain Tumors. Asian Pac J Cancer Prev, 14, 4101-6. https://doi.org/10.7314/APJCP.2013.14.7.4101
  38. Unal D, Oguz A, Acmaz B, et al (2014). Lack of any Association between Season of Diagnosis and Survival of Gastric Cancer Cases in Kayseri, Turkey. Asian Pac J Cancer Prev, 15, 1763-6. https://doi.org/10.7314/APJCP.2014.15.4.1763
  39. Wu Q, Zhao YB, Sun ZH, et al (2013). Clinical application of endoscopic inguinal lymph node resection after lipolysis and liposuction for vulvar cancer. Asian Pac J Cancer Prev, 14, 7121-6. https://doi.org/10.7314/APJCP.2013.14.12.7121
  40. Wu XY, Huang XE, You SX, et al (2013). Phase II Study of pemetrexed as second or third line combined chemotherapy in patients with colorectal cancer. Asian Pac J Cancer Prev, 14, 2019-22. https://doi.org/10.7314/APJCP.2013.14.3.2019
  41. Wei GL, Huang XE, Huo JG, et al (2013). Phase II Study on pemetrexed-based chemotherapy in treating patients with metastatic gastric cancer not responding to prior palliative chemotherapy. Asian Pac J Cancer Prev, 14, 2703-6. https://doi.org/10.7314/APJCP.2013.14.5.2703
  42. Xu C, Huang XE, Wang SX, et al (2014). Drainage alone or combined with anti-tumor therapy for treatment of obstructive jaundice caused by recurrence and metastasis after primary tumor Resection. Asian Pac J Cancer Prev, 15, 2681-4. https://doi.org/10.7314/APJCP.2014.15.6.2681
  43. Xu C, Lv PH, Huang XE, et al (2014). Safety and efficacy of sequential transcatheter arterial chemoembolization and portal vein embolization prior to major hepatectomy for patients with HCC. Asian Pac J Cancer Prev, 15, 703-6. https://doi.org/10.7314/APJCP.2014.15.2.703
  44. Xu X, Wang L, Xu HQ, et al (2013). Clinical comparison between paclitaxel liposome (Lipusu(R)) and paclitaxel for treatment of patients with metastatic gastric cancer. Asian Pac J Cancer Prev, 14, 2591-4. https://doi.org/10.7314/APJCP.2013.14.4.2591
  45. Yan HA, Shen K, Huang XE (2013). Clinical study on mannan peptide combined with TP regimen in treating patients with non-small cell lung cancer. Asian Pac J Cancer Prev, 14, 4801-4. https://doi.org/10.7314/APJCP.2013.14.8.4801
  46. Yang L, Parkin DM, Ferlay J, Li L, Chen Y (2005). Estimates of cancer incidence in China for 2000 and projections for 2005. Cancer Epidemiol Biomarkers Prev, 14, 43-250.
  47. Yang L, Huang XE, Xu L, et al (2013). Acidic pelvic drainage as a predictive factor for anastomotic leakage after surgery for patients with rectal cancer. Asian Pac J Cancer Prev, 14, 5441-7. https://doi.org/10.7314/APJCP.2013.14.9.5441
  48. Yang L, Huang XE, Xu L, et al (2013). Role of MYH polymorphisms in sporadic colorectal cancer in China: a case-control, population-based study. Asian Pac J Cancer Prev, 14, 6403-9. https://doi.org/10.7314/APJCP.2013.14.11.6403
  49. Yang L, Huang XE, Zhou JN (2013), Risk assessment on anastomotic leakage after rectal cancer surgery: an analysis of 753 patients. Asian Pac J Cancer Prev, 14, 4447-53. https://doi.org/10.7314/APJCP.2013.14.7.4447
  50. Yang TF, Guo L, Wang Q (2014). Meta-analysis of associations between four polymorphisms in the matrix metalloproteinases gene and gastric cancer risk. Asian Pac J Cancer Prev, 15, 1263-7. https://doi.org/10.7314/APJCP.2014.15.3.1263
  51. Yin HT, Zhang DG, Wu XL (2013). In vivo evaluation of curcumin-loaded nanoparticles in a A549 xenograft mice model. Asian Pac J Cancer Prev, 14, 409-12. https://doi.org/10.7314/APJCP.2013.14.1.409
  52. Yin HT, Tian QZ, Guan L (2013). In vitro and in vivo evaluation of the antitumor efficiency of resveratrol against lung cancer. Asian Pac J Cancer Prev, 14 , 1703-6. https://doi.org/10.7314/APJCP.2013.14.3.1703
  53. Zhang Q, Shan C, Wu P, et al (2014). Clinical value of dual-phase 18F-FDG SPECT with serum procalcitonin for identification of etiology in tumor patients with fever of unknown origin. Asian Pac J Cancer Prev, 15, 683-6. https://doi.org/10.7314/APJCP.2014.15.2.683
  54. Zhou RP, Chen G, Shen ZL, et al (2014). Cinobufacin suppresses cell proliferation via miR-494 in BGC- 823 gastric cancer cells. Asian Pac J Cancer Prev, 15, 1241-5. https://doi.org/10.7314/APJCP.2014.15.3.1241

Cited by

  1. Synthesized tetrahydroisoquinoline alkaloid exerts anticancer effects at least in part by suppressing NF-κB-regulated proteins in A549 human lung cancer cells vol.33, pp.3, 2014, https://doi.org/10.3892/or.2014.3658
  2. Peroxisome Proliferator-Activated Receptor-Gamma Pro12Ala Polymorphism Could be a Risk Factor for Gastric Cancer vol.16, pp.6, 2015, https://doi.org/10.7314/APJCP.2015.16.6.2333
  3. Value of Combined Detection of Serum CEA, CA72-4, CA19-9 and TSGF in the Diagnosis of Gastric Cancer vol.16, pp.9, 2015, https://doi.org/10.7314/APJCP.2015.16.9.3867
  4. Toosendanin inhibits growth and induces apoptosis in colorectal cancer cells through suppression of AKT/GSK-3β/β-catenin pathway vol.47, pp.5, 2015, https://doi.org/10.3892/ijo.2015.3157
  5. Tetramethylpyrazine-mediated regulation of CXCR4 in retinoblastoma is sensitive to cell density vol.15, pp.5, 2017, https://doi.org/10.3892/mmr.2017.6293
  6. Tetramethylpyrazine inhibits prostate cancer progression by downregulation of forkhead box M1 vol.38, pp.2, 2017, https://doi.org/10.3892/or.2017.5768
  7. Tetramethylpyrazine suppresses lipid accumulation in macrophages via upregulation of the ATP-binding cassette transporters and downregulation of scavenger receptors vol.38, pp.4, 2017, https://doi.org/10.3892/or.2017.5881
  8. Ethanol extract of Antrodia camphorata inhibits proliferation of HCT-8 human colorectal cancer cells by arresting cell cycle progression and inducing apoptosis vol.16, pp.4, 2017, https://doi.org/10.3892/mmr.2017.7207