Acquired cisplatin resistance in human lung adenocarcinoma cells is associated with enhanced autophagy.
Activation of autophagy is a hallmark in tumor cells treated with chemotherapy, but the role of autophagy in acquired resistance of lung adenocarcinoma to cisplatin-based chemotherapy remains to be clarified. Our aim was to address that question by surveying the autophagic activity in parental lung adenocarcinoma cell line A549 and its 8-fold, more resistant subcell line, A549/DDP, which was obtained by treating cisplatin with increasing concentrations. A549/DDP and A549 cells were exposed to serum-free culture medium or ionizing radiation. To measure the stress-induced autophagy, LC3-II, as an autophagosome marker, was measured by immunofluorescence and Western blotting. To determine the effect of 3-MA, a known inhibitor of autophagy, on overcoming acquired cisplatin resistance, the MTT assay and flow cytometry were performed. Western blotting analysis demonstrated that LC3-II was increased in A549/DDP cells, compared with those of parental A549 cells, under stress conditions. Meanwhile, immunofluorescence staining showed that LC3-II protein was located mainly in the cytoplasm of A549/DDP. We also found that 3-MA can enhance the growth inhibition and apoptotic effect of cisplatin in acquired resistant cells (A549/DDP). Collectively, our results provide evidence that the upregulation of autophagy plays a major role in cisplatin resistance of A549/DDP cells.
Ren
Jing-Hua
JH
Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
He
Wen-Shan
WS
Nong
Li
L
Zhu
Qing-Yao
QY
Hu
Kai
K
Zhang
Rui-Guang
RG
Huang
Li-Li
LL
Zhu
Fang
F
Wu
Gang
G
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001343:Autophagy / Q000187:drug effects / Q000502:physiology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D006801:Humans
D000970:Antineoplastic Agents; D002945:Cisplatin