• Molecules and Cells
• /
• 제37권9호
• /
• pp.664-671
• /
• 2014

MiR-217 can function as an oncogene or a tumour suppressor gene depending on cell type. However, the function of miR-217 in lung cancer remains unclear to date. This study aims to evaluate the function of miR-217 in lung cancer and investigate its effect on the sensitivity of lung cancer cells to cisplatin. The expression of miR-217 was detected in 100 patients by real-time PCR. The effects of miR-217 overexpression on the proliferation, apoptosis, migration and invasion of SPC-A-1 and A549 cells were investigated. The target gene of miR-217 was predicted by Targetscan online software, screened by dual luciferase reporter gene assay and demonstrated by Western blot. Finally, the effects of miR-217 up-regulation on the sensitivity of A549 cells to cisplatin were determined. The expression of miR-217 was significantly lower in lung cancer tissues than in noncancerous tissues (p < 0.001). The overexpression of miR-217 significantly inhibited the proliferation, migration and invasion as well as promoted the apoptosis of lung cancer cells by targeting KRAS. The up-regulation of miR-217 enhanced the sensitivity of SPC-A-1 and A549 cells to cisplatin. In conclusion, miR-217 suppresses tumour development in lung cancer by targeting KRAS and enhances cell sensitivity to cisplatin. Our results encourage researchers to use cisplatin in combination with miR-217 to treat lung cancer. This regime might lead to low-dose cisplatin application and cisplatin side-effect reduction.

• Asian Pacific Journal of Cancer Prevention
• /
• 제15권6호
• /
• pp.2511-2515
• /
• 2014

Objective: Lung cancer is one of the malignant tumors with greatest morbidity and mortality around the world. The keys to targeted therapy are discovery of lung cancer biomarkers to facilitate improvement of survival and quality of life for the patients with lung cancer. Translationally controlled tumor protein (TCTP) is one of the most overexpressed proteins in human lung cancer cells by comparison to the normal cells, suggesting that it might be a good biomarker for lung cancer. Materials and Methods: In the present study, the targeted efficacy of dihydroartemisinin (DHA) on TCTP expression in the A549 lung cancer cell model was explored. Results and Conclusions: DHA could inhibit A549 lung cancer cell proliferation, and simultaneously up-regulate the expression of TCTP mRNA, but down-regulate its protein expression in A549 cells. In addition, it promoted TCTP protein secretion. Therefore, TCTP might be used as a potential biomarker and therapeutic target for non-small cell lung cancers.

• Tuberculosis and Respiratory Diseases
• /
• 제60권6호
• /
• pp.663-672
• /
• 2006

연구배경: 미세먼지는 여러 가지 유기물과 무기물의 복합체로 그 구성 성분이 시간과 장소에 따라 다르고 모양과 크기도 일정하지 않으며, 특히 지름 $10{\mu}m$이하의 미세먼지 (particulate matter 10; $PM_{10}$)는 흡입이 가능한 입자의 크기여서 하부기관지 및 폐의 가스-교환부분까지 침착하여 호흡기계에 손상을 일으킬 수 있다. 본 연구에서는 황사에 포함된 $PM_{10}$과 비황사 시기에 포집된 $PM_{10}$이 폐상피세포주에 작용하여 전염증성 사이토카인(proinflammatory cytokine) 및 cytokine messenger RNA(mRNA)의 발현에 어떤 영향이 있는지를 관찰하여 기관지 천식과 만성 폐쇄성 폐질환등 호흡기 질환의 증상 악화기전에 미치는 역할을 규명하고자 하였다. 연구방법: 공기 포집기(HV 500F, sibata model)를 이용하여 황사와 비황사 기간에 하루 6시간씩 실외의 장소에서 대기분진을 membrane filter에 포집한 다음, $PM_{10}$입자를 추출하고 폐암 상피세포주인 A549 cells(한국세포은행주)에 $PM_{10}$을 농도에 맞게($10{\mu}g/ml$, $100{\mu}g/ml$, $500{\mu}g/ml$) 노출시켰다. 각각의 노출된 세포로부터 interleukin(IL)-$1{\alpha}$, $IL-1{\beta}$, IL-8, granulocyte macrophage colony stimulating factor(GM-CSF)의 mRNA를 역전사중합효소연쇄반응(reverse transcriptase polymerase chain reaction; RT-PCR) 방법으로 측정하였다. 결 과: 황사 및 비황사 기간 중 포집된 $PM_{10}$을 가했을 시 가하지 않은 대조군에 비하여 $IL-1{\alpha}$, $IL-1{\beta}$, IL-8, granulocyte macrophage colony stimulating factor (GM-CSF)의 m'RNA와 cytokine의 발현이 유의하게 높았으며, 황사 기간의 고농도의 $PM_{10}$에 노출된 세포의 $IL-1{\alpha}$ mRNA는 비황사 기간의 $PM_{10}$에 노출된 세포의 mRNA보다 증가되어 있었다. 결 론: $PM_{10}$은 A549 cells에서 전염증성 사이토카인의 발현을 증가시키고 비황사 기간보다 황사 기간 중 대기 중에서 채취한 $PM_{10}$에 노출된 A549 cells에서 일부의 전염증성 사이토카인의 mRNA발현을 더욱 증가시키는 것을 알 수 있었다. 따라서 황사 기간의 $PM_{10}$에 의한 일부의 전염증성 사이토카인의 발현 증가가 만성 호흡기 질환의 증상 악화기전에 연관되어 있을 가능성을 시사하였다.

• 한국원자력학회:학술대회논문집
• /
• 한국원자력학회 2004년도 추계학술발표회 발표논문집
• /
• pp.1138-1139
• /
• 2004

• 동의생리병리학회지
• /
• 제17권3호
• /
• pp.677-683
• /
• 2003

We investigated the effects of Insamsapye-tang (ISSPT) water extract on the growth of human lung carcinoma A549 cells. Upon treatment with ISSPT extract, a concentration-dependent inhibition of cell viability was observed and cells developed many of the hallmark features of apoptosis, including condensation of chromatin. Flow cytometry analysis confirmed that ISSPT treatment increased populations of apoptotic-sub G1 phase. In addition, proteolytic degradation of poly(ADP-ribose) polymerase (PARP) and β-catenin protein were observed after treatment of ISSPT extract. These apoptotic effects of ISSPT in A549 cells were associated with marked inhibition of Bel-xL expression in a dose-dependent manner, however the levels of Bcl-2 and Bax expression were not affected. ISSPT treatment also induced the expression of tumor suppressor p53 mRNA and inhibited the expression of caspase-3 mRNA. The previous and present results indicated that ISSPT-induced inhibition of lung cancer cell proliferation is associated with the blockage of G1/S progression and the induction of apoptosis.

• Integrative Medicine Research
• /
• 제3권2호
• /
• pp.67-73
• /
• 2014

Background: The transcription factor signal transducer and activator of transcription 3 (Stat3)is constitutively activated in many human cancers. It promotes tumor cell proliferation,inhibits apoptosis, induces angiogenesis and metastasis, and suppresses antitumor hostimmune responses. Therefore, Stat3 has emerged as a promising molecular target for cancertherapies. In this study, we evaluated the Stat3-suppressive activity of 38 herbal medicinestraditionally used in Korea.Methods: Medicinal herb extracts in 70% ethanol were screened for their ability to suppressStat3 in the A549 human lung cancer cell line. A Stat3-responsive reporter assay system wasused to detect intracellular Stat3 activity in extract-treated cells, and Western blot analyseswere performed to measure the expression profiles of Stat3-regulated proteins.Results: Fifty percent of the 38 extracts possessed at least mild Stat3-suppressive activities(i.e., activity less than 75% of the vehicle control). Ethanol extracts of Bupleurum falcatumL., Taraxacum officinale Weber, Solanum nigrum L., Ulmus macrocarpa Hance, Euonymus alatusSieb., Artemisia capillaris Thunb., and Saururus chinensis (Lour.) Baill inhibited up to 75% of thevehicle control Stat3 activity level. A549 cells treated with these extracts also had reducedBcl-xL, Survivin, c-Myc, and Mcl-1 expression.Conclusion: Many medicinal herbs traditionally used in Korea contain Stat3 activity-suppressing substances. Because of the therapeutic impact of Stat3 inhibition, these resultscould be useful when developing novel cancer therapeutics from medicinal herbs.

• Molecules and Cells
• /
• 제42권4호
• /
• pp.321-332
• /
• 2019

The brain is the most common metastatic site of lung adenocarcinoma; however, the mechanism of this selective metastasis remains unclear. We aimed to verify the hypothesis that exposure of tumor cells to the brain microenvironment leads to changes in their gene expression, which promotes their oriented transfer to the brain. A549 and H1299 lung adenocarcinoma cells were exposed to human astrocyte-conditioned medium to simulate the brain microenvironment. Microarray analysis was used to identify differentially expressed genes, which were confirmed by quantitative real-time PCR and western blotting. Knockdown experiments using microRNAs and the overexpression of genes by cell transfection were performed in addition to migration and invasion assays. In vitro findings were confirmed in clinical specimens using immunohistochemistry. We found and confirmed a significant increase in insulin-like growth factor binding protein-3 (IGFBP3) levels. Our results also showed that the up-regulation of IGFBP3 promoted A549 cell epithelial-mesenchymal transition, migration, and invasion, while the knockdown of IGFBP3 resulted in decreased cell motility. We also found that Transforming growth factor-${\beta}$ (TGF-${\beta}$)/Mothers against decapentaplegic homolog 4 (Smad4)-induced epithelial-mesenchymal transition was likely IGFBP3-dependent in A549 cells. Finally, expression of IGFBP3 was significantly elevated in pulmonary cancer tissues and intracranial metastatic tissues. Our data indicate that up-regulation of IGFBP3 might mediate brain metastasis in lung adenocarcinoma, which makes it a potential therapeutic target.

• Asian Pacific Journal of Cancer Prevention
• /
• 제16권7호
• /
• pp.3035-3042
• /
• 2015

Background: Isorhamnetin (Iso), a novel and essential monomer derived from total flavones of Hippophae rhamnoides that has long been used as a traditional Chinese medicine for angina pectoris and acute myocardial infarction, has also shown a spectrum of antitumor activity. However, little is known about the mechanisms of action Iso on cancer cells. Objectives: To investigate the effects of Iso on A549 lung cancer cells and underlying mechanisms. Materials and Methods: A549 cells were treated with $10{\sim}320{\mu}g/ml$ Iso. Their morphological and cellular characteristics were assessed by light and electronic microscopy. Growth inhibition was analyzed by MTT, clonogenic and growth curve assays. Apoptotic characteristics of cells were determined by flow cytometry (FCM), DNA fragmentation, single cell gel electrophoresis (comet) assay, immunocytochemistry and terminal deoxynucleotidyl transferase nick end labeling (TUNEL). Tumor models were setup by transplanting Lewis lung carcinoma cells into C57BL/6 mice, and the weights and sizes of tumors were measured. Results: Iso markedly inhibited the growth of A549 cells with induction of apoptotic changes. Iso at $20{\mu}g/ml$, could induce A549 cell apoptosis, up-regulate the expression of apoptosis genes Bax, Caspase-3 and P53, and down-regulate the expression of Bcl-2, cyclinD1 and PCNA protein. The tumors in tumor-bearing mice treated with Iso were significantly smaller than in the control group. The results of apoptosis-related genes, PCNA, cyclinD1 and other protein expression levels of transplanted Lewis cells were the same as those of A549 cells in vitro. Conclusions: Iso, a natural single compound isolated from total flavones, has antiproliferative activity against lung cancer in vitro and in vivo. Its mechanisms of action may involve apoptosis of cells induced by down-regulation of oncogenes and up-regulation of apoptotic genes.

• 대한약학회:학술대회논문집
• /
• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
• /
• pp.244.1-244.1
• /
• 2002

Cyclooxygenase-2 ( COX-2 ) is an inducible enzyme which produces prostanoids by various stimuli. Overexpression of COX-2 in many tumor types indicates its association with tumor progression, which has been a promising target for chemoprevention and chemomodulation. We studied conc- and time-dependency of COX-2 inhibition, growth inhibition, and cell cycle arrest induced by celecoxib, a selective COX-2 inhibitor, in human non-small cell lung cancer (NSCLC) A549 cells. (omitted)

• 생명과학회지
• /
• 제26권11호
• /
• pp.1320-1329
• /
• 2016

본 연구는 다당체의 한 종류인 penta-O-galloyl-${\beta}$-D-glucose (PGG)가 사람의 여러 조직에서 기원하는 여러 암세포주(A-549, MDA-MB-231, U87-MG, MCF-7 및 PANC-1), 정상 MRC-5 태아 섬유아세포 그리고 사랑니에서 유래한 간엽줄기세포(DPSCs)에 미치는 세포독성 효과를 조사하였다. $IC_{50}$값은 다른 세포주에 비해 높은 증식률을 나타내는 A-549 및 MDA-MB-231 암세포주에서 유의적으로 낮게 관찰되었다. 10 uM의 PGG가 포함된 배양액에서 세포를 7일 동안 배양한 결과, 세포배가시간은 모든 세포주에서 유의적으로 늘어났고, 세포배가시간과 $IC_{50}$값의 관계를 조사한 결과, 세포배가시간이 늘어남에 따라 $IC_{50}$값은 비례적으로 증가됨을 증명하였다. 또한, 10 uM의 PGG로 처리된 세포주들은 노화와 관련된 ${\beta}-galactosidase$의 활성도가 높게 관찰되었다. 특히, telomerase 활성도는 A-549 및 MDA-MB-231 암세포주에서 다른 세포주에 비하여 현저히 감소하는 것을 관찰하였다. 이러한 결과를 바탕으로 PGG는 높은 증식률을 보이는 암세포주에서 높은 세포독성효과를 나타내어 잠재적인 항암물질임을 증명하였다.