Overexpression of caveolin-1 reduces Taxol resistance in human osteosarcoma cells by attenuating PI3K-Akt-JNK dependent autophagy.

作者: Jian Guan , Zhenchao Yuan , Juliang He , Zhenjie Wu , Bin Liu

DOI: 10.3892/ETM.2016.3713

关键词: OsteosarcomaDownregulation and upregulationCellPI3K/AKT/mTOR pathwayCell cycleMTT assayAutophagyCancer researchViability assayMolecular biologyBiology

摘要: Caveolin-1 (CAV-1), which is an oncoprotein and a tumor suppressor, highly expressed in normal osteoblasts. Although researchers have investigated its role human osteosarcoma, the mechanism of caveolin-1 action osteosarcoma remains unknown. In present study, Saos-2 U-2 OS cells were cultured with continuous induction protocol gradually increasing Taxol concentration for 6 months to establish drug-resistant cell lines. CAV-1 expression levels detected via western blotting quantitative polymerase chain reaction. knockdown was achieved using short hair-pin RNA lentivirus vector, viability analyzed by MTT assay. The effect on autophagy investigated, downregulation increased identified Taxol-resistant cells. addition, results study demonstrated that promotes induces resistance Taxol. Notably, overexpression resensitized declined autophagy. conclusion, be downregulated cells, suppressed attenuating PI3K-Akt-JNK-dependent findings suggest further investigation into CAV-1's warranted. future, detection may used as indicator evaluate treatment prognosis patients osteosarcoma.

参考文章(28)
Yin Shi, Shi-Hao Tan, Shukie Ng, Jing Zhou, Na-Di Yang, Gi-Bang Koo, Kerrie-Ann McMahon, Robert G Parton, Michelle M Hill, Miguel A Del Pozo, You-Sun Kim, Han-Ming Shen, None, Critical role of CAV1/caveolin-1 in cell stress responses in human breast cancer cells via modulation of lysosomal function and autophagy. Autophagy. ,vol. 11, pp. 769- 784 ,(2015) , 10.1080/15548627.2015.1034411
Nian-Kang Sun, Shang-Lang Huang, Hsing-Pang Lu, Ting-Chang Chang, Chuck C-K Chao, None, Integrative transcriptomics-based identification of cryptic drivers of taxol-resistance genes in ovarian carcinoma cells: Analysis of the androgen receptor Oncotarget. ,vol. 6, pp. 27065- 27082 ,(2015) , 10.18632/ONCOTARGET.4824
Suning Chen, Xingmei Zhu, Hongyu Qiao, Mingxiang Ye, Xiaofeng Lai, Shentong Yu, Likun Ding, Aidong Wen, Jian Zhang, Protective autophagy promotes the resistance of HER2-positive breast cancer cells to lapatinib Tumor Biology. ,vol. 37, pp. 2321- 2331 ,(2016) , 10.1007/S13277-015-3800-9
Sandy Giuliano, Yann Cormerais, Maeva Dufies, Renaud Grépin, Pascal Colosetti, Amine Belaid, Julien Parola, Anthony Martin, Sandra Lacas-Gervais, Nathalie M Mazure, Rachid Benhida, Patrick Auberger, Baharia Mograbi, Gilles Pagès, Resistance to sunitinib in renal clear cell carcinoma results from sequestration in lysosomes and inhibition of the autophagic flux Autophagy. ,vol. 11, pp. 1891- 1904 ,(2015) , 10.1080/15548627.2015.1085742
Adam S Crystal, Alice T Shaw, Lecia V Sequist, Luc Friboulet, Matthew J Niederst, Elizabeth L Lockerman, Rosa L Frias, Justin F Gainor, Arnaud Amzallag, Patricia Greninger, Dana Lee, Anuj Kalsy, Maria Gomez-Caraballo, Leila Elamine, Emily Howe, Wooyoung Hur, Eugene Lifshits, Hayley E Robinson, Ryohei Katayama, Anthony C Faber, Mark M Awad, Sridhar Ramaswamy, Mari Mino-Kenudson, A John Iafrate, Cyril H Benes, Jeffrey A Engelman, None, Patient-derived models of acquired resistance can identify effective drug combinations for cancer Science. ,vol. 346, pp. 1480- 1486 ,(2014) , 10.1126/SCIENCE.1254721
Karen N. Wu, Maria Queenan, Jonathan R. Brody, Magdalena Potoczek, Federica Sotgia, Michael P. Lisanti, Agnieszka K. Witkiewicz, Loss of stromal caveolin-1 expression in malignant melanoma metastases predicts poor survival. Cell Cycle. ,vol. 10, pp. 4250- 4255 ,(2011) , 10.4161/CC.10.24.18551
Lorenzo Galluzzi, Federico Pietrocola, Beth Levine, Guido Kroemer, Metabolic Control of Autophagy Cell. ,vol. 159, pp. 1263- 1276 ,(2014) , 10.1016/J.CELL.2014.11.006
Augustine MK Choi, Stefan W Ryter, Beth Levine, None, Autophagy in human health and disease. The New England Journal of Medicine. ,vol. 368, pp. 1845- 1846 ,(2013) , 10.1056/NEJMC1303158
Fan Zhang, Masafumi Kumano, Eliana Beraldi, Ladan Fazli, Caigan Du, Susan Moore, Poul Sorensen, Amina Zoubeidi, Martin E. Gleave, Clusterin facilitates stress-induced lipidation of LC3 and autophagosome biogenesis to enhance cancer cell survival. Nature Communications. ,vol. 5, pp. 5775- 5775 ,(2014) , 10.1038/NCOMMS6775
Michelle Cicchini, Rumela Chakrabarti, Sameera Kongara, Sandy Price, Ritu Nahar, Fred Lozy, Hua Zhong, Alexei Vazquez, Yibin Kang, Vassiliki Karantza, Autophagy regulator BECN1 suppresses mammary tumorigenesis driven by WNT1 activation and following parity Autophagy. ,vol. 10, pp. 2036- 2052 ,(2014) , 10.4161/AUTO.34398