DOI QR코드

DOI QR Code

Tumor Inhibition Effects and Mechanisms of Angelica sinensis and Sophorae flavescentis ait Decoction Combined with Cisplatin in Xenograft Mice

  • Yan, De-Qi (Gansu Traditional Chinese Medicine College) ;
  • Liu, Yong-Qi (Gansu Traditional Chinese Medicine College) ;
  • Li, Ying-Dong (Gansu Traditional Chinese Medicine College) ;
  • Li, Dou (Gansu Traditional Chinese Medicine College) ;
  • Cheng, Xiao-Li (Gansu Traditional Chinese Medicine College) ;
  • Wu, Zhi-Wei (Gansu Traditional Chinese Medicine College)
  • Published : 2014.06.15

Abstract

Background: To investigate tumor inhibition effects and mechanisms of Angelica sinensis and Sophorae flavescentis ait decoction (ASSF) combined with diamine-dichloroplatinum (DDP). Materials and Methods: Bodyweight, tumor inhibition rate and q value were calculated for single ASSF or ASSF combined with DDP on H22 carcinoma xenograft KM mice. Biochemical methods for serum LDH, AST, ALT, and AKP, ELISA method for serum HIF-$1{\alpha}$, pathological assessemnt of thymus, immunohistochemistry detection of tumor tissue caspase3 and mutant p53 protein, and qRT-PCR detection of bax/ bcl-2 mRNA were applied. Results: Compared with DDP control group, the bodyweight increased in ASSF-DDP group (p<0.01). Tumor inhibition rates for DDP, ASSF, ASSF-DDP were 62.7%. 43.7% and 71.0% respectively, with a q value of 0.90. Compared with other groups, thymus of DDP control group had obvious pathological injury (p<0.01), serum LDH, AST, ALT, AKP increased significantly in DDP control group (p<0.01), while serum HIF-$1{\alpha}$ was increased in the model control group. Compared with this latter, the expression of mutant p53 protein and bcl-2 mRNA were decreased in all treatment groups (p<0.01), but there were no statistical difference between DDP control p and ASSF-DDP groups. The expression of caspase3 protein and bax mRNA was increased in all treatment groups, with statistical differences between the DDP and ASSF-DDP groups (p<0.01). Conclusions: ASSF can inhibit bodyweight decrease caused by DDP, can inhibit tumor growth synergistically with DDP mainly through increasing serum HIF-$1{\alpha}$ and pro-apoptotic molecules such as caspase 3 and bax, rather than through decreasing anti-apoptotic mutant p53 and bcl-2. ASSF can reduce DDP toxicity due to decreasing the release of LDH, AST, ALT, AKP into blood and enhancing thymus protection.

Keywords

References

  1. Bentli R, Parlakpinar H, Polat A, et al (2013). Molsidomine prevents cisplatin- induced hepatotoxicity. Arch Med Res, 44, 521-8. https://doi.org/10.1016/j.arcmed.2013.09.013
  2. Chang C, Liu SP, Fang CH, et al (2013). Effects of matrine on the proliferation of HT29 human colon cancer cells and its antitumor mechanism. Oncol Lett, 6, 699-704.
  3. Chen H, Zhang J, Luo J, et al (2013). Antiangiogenic effects of oxymatrine on pancreatic cancer by inhibition of the NF-${\kappa}B$-mediated VEGF signaling pathway. Oncol Rep, 30, 589-95.
  4. Duval M, Daniel SJ (2012). Meta-analysis of the efficacy of amifostine in the prevention of cisplatin ototoxicity. J Otolaryngol Head Neck Surg, 41, 309-15.
  5. Gao M, Zhang JH, Zhou FX, et al (2012). Angelica sinensis suppresses human lung adenocarcinoma A549 cell metastasis by regulating MMPs/TIMPs and TGF-$\beta$1. Oncol Rep, 27, 585-93.
  6. Garcia MM, Acquier A, Suarez G, et al (2012). Cisplatin inhibits testosterone synthesis by a mechanism that includes the action of reactive oxygen species (ROS) at the level of P450scc. Chem Biol Interact. 199:185-91. https://doi.org/10.1016/j.cbi.2012.08.012
  7. Hoda E. Mohamed, Sahar E. El-Swefy, et al (2013). Effect of erythropoietin therapy on the progression of cisplatin induced renal injury in rats. Exp Toxicol Pathol, 65 197-203. https://doi.org/10.1016/j.etp.2011.08.006
  8. Hossein K, Elmira G, Mojgan A, et al (2014). ALDH1 in combination with CD44 as putative cancer stem cell markers are correlated with poor prognosis in urothelial carcinoma of the urinary bladder. Asian Pac J Cancer Prev, 15, 2013-20. https://doi.org/10.7314/APJCP.2014.15.5.2013
  9. Jin H, Sun Y, Wang S, et al (2013). Matrine sctivates PTEN to induce growth inhibition and apoptosis in V600EBRAF harboring melanoma cells. Int J Mol Sci, 14, 16040-57. https://doi.org/10.3390/ijms140816040
  10. Jung HI, Jo MJ, Kim HR, et al (2014). Extract of Saccharina japonica induces apoptosis companied by cell cycle arrest and endoplasmic reticulum stress in SK-Hep1 human hepatocellular carcinoma cells. Asian Pac J Cancer Prev, 15, 2993-9. https://doi.org/10.7314/APJCP.2014.15.7.2993
  11. Lee JG, Hsieh WT, Chen SU, Chiang BH (2012). Hematopoietic and myeloprotective activities of an acidic Angelica sinensis polysaccharide on human CD34+ stem cells. J Ethnopharmacol, 139, 739-45. https://doi.org/10.1016/j.jep.2011.11.049
  12. Lee YY, Mok MT, Cheng AS (2014). Dissecting the pleiotropic actions of HBx mutants against hypoxia in hepatocellular carcinoma. Hepatobiliary Surg Nutr, 3, 95-7.
  13. Li HJ, Wang JM, Tian YT, et al (2013). Effect of matrine on Fas, VEGF, and activities of telomerase of MCF-7 cells. Zhongguo Zhong Xi Yi Jie He Za Zhi, 33, 1247-51.
  14. Lin YL, Lai WL, Harn HJ, et al (2013). The methanol extract of Angelica sinensis induces cell apoptosis and suppresses tumor growth in human malignant brain tumors. Evid Based Complement Alternat Med, 2013, 394636.
  15. Liu J, Xu CY, Cai SZ, et al (2013). Senescence effects of Angelica sinensis polysaccharides on human acute myelogenous leukemia stem and progenitor cells. Asian Pac J Cancer Prev, 14, 6549-56. https://doi.org/10.7314/APJCP.2013.14.11.6549
  16. Liu S, Cao M, Li D, et al (2011). Purification and anticancer activity investigation of pentacyclic triterpenoids from the leaves of Sinojackia sarcocarpa L.Q. Luo by high-speed counter-current chromatography. Nat Prod Res, 25, 1600-6. https://doi.org/10.1080/14786419.2010.496115
  17. Liu Y, Li Y, Qin J, et al (2014). Matrine reduces proliferation of human lung cancer cells by inducing apoptosis and changing miRNA expression profiles. Asian Pac J Cancer Prev, 15, 2169-77. https://doi.org/10.7314/APJCP.2014.15.5.2169
  18. Lovine B, Oliviero G, Garofalo M, et al(2014). The Anti-Proliferative Effect of L-Carnosine Correlates with a Decreased Expression of Hypoxia Inducible Factor 1 alpha in Human Colon Cancer Cells. PLoS One, 9, 96755. https://doi.org/10.1371/journal.pone.0096755
  19. Palipoch S, Punsawad C, Koomhin P, et al (2014). Hepatoprotective effect of curcumin and alpha-tocopherol against cisplatin-induced oxidative stress. BMC Complement Altern Med, 14, 111. https://doi.org/10.1186/1472-6882-14-111
  20. Pu LP, Chen HP, Cao MA, et al(2013). The antiangiogenic activity of Kushecarpin D, a novel flavonoid isolated from Sophora flavescens Ait. Life Sci, 93, 791-7. https://doi.org/10.1016/j.lfs.2013.09.025
  21. Rasul A, Yu B, Yang LF, et al (2011). Induction of mitochondria-mediated apoptosis in human gastric adenocarcinoma SGC-7901 cells by kuraridin and Nor-kurarinone isolated from Sophora flavescens. Asian Pac J Cancer Prev, 12, 2499-504.
  22. Rjiba-Touati K, Ayed-Boussema I, Skhiri H, et al (2012). Induction of DNA fragmentation, chromosome aberrations and micronuclei by cisplatin in rat bone-marrow cells: Protective effect of recombinant human erythropoietin . Mutat Res, 747, 202-6. https://doi.org/10.1016/j.mrgentox.2012.05.011
  23. Saw CL, Wu Q, Su ZY, et al (2013). Effects of natural phytochemicals in Angelica sinensis (Danggui) on Nrf2-mediated gene expression of phase II drug metabolizing enzymes and anti-inflammation. Biopharm Drug Dispos, 34, 303-11. https://doi.org/10.1002/bdd.1846
  24. Song HY, Deng XH, Yuan GY, et al (2014). Expression of bcl-2 and p53 in induction of esophageal cancer cell apoptosis by ECRG2 in combination with cisplatin. Asian Pac J Cancer Prev, 15, 1397-401. https://doi.org/10.7314/APJCP.2014.15.3.1397
  25. Song K, Li M, Xu XJ, et al (2014). HIF-1$\alpha$ and GLUT1 gene expression is associated with chemoresistance of acute myeloid leukemia. Asian Pac J Cancer Prev, 15, 1823-9. https://doi.org/10.7314/APJCP.2014.15.4.1823
  26. Valentovic MA, Ball JG, Brown JM, et al (2014). Resveratrol attenuates cisplatin renal cortical cytotoxicity by modifying oxidative stress. Toxicol In Vitro, 28, 248-57. https://doi.org/10.1016/j.tiv.2013.11.001
  27. Wang Y, Han C, Fang X, et al (2013). Effect of Kushen (Radix Sophorae flavescentis) extract on laryngeal neoplasm Hep2 cells. J Tradit Chin Med, 33, 218-22. https://doi.org/10.1016/S0254-6272(13)60128-4
  28. Yu Hui-Min, Wang Tsing-Cheng (2012). Mechanism of cisplatin resistance in human urothelial carcinoma cells. Food Chem Toxicol, 50, 1226-37. https://doi.org/10.1016/j.fct.2012.01.040
  29. Xie CH, Zhang MS, Zhou YF, et al (2006). Chinese medicine Angelica sinensis suppresses radiation-induced expression of TNF-alpha and TGF-beta1 in mice. Oncol Rep, 15, 1429-36.
  30. Zhang HM, Wang XY, Wang XM, et al (2012). Inhibition of Lycium barbarum polysaccharide on transplanted liver cancer in mice. Chinese Traditional Herbal Drugs, 43, 1142-6.
  31. Zhang YS, Jiang G, Gao H, et al (2014). Influence of ionizing radiation on ovarian carcinoma SKOV- 3 xenografts in nude mice under hypoxic conditions. Asian Pac J Cancer Prev, 15, 2353-8. https://doi.org/10.7314/APJCP.2014.15.5.2353
  32. Zhou H, Xu M, Gao Y, et al (2014). Matrine induces caspase-independent program cell death in hepatocellular carcinoma through bid-mediated nuclear translocation of apoptosis inducing factor. Mol Cancer, 13, 59. https://doi.org/10.1186/1476-4598-13-59

Cited by

  1. Monosaccharide composition analysis of immunomodulatory polysaccharides by on-line hollow fiber microextraction with high-performance liquid chromatography vol.39, pp.5, 2016, https://doi.org/10.1002/jssc.201501205