Cisplatin suppresses tumor proliferation by inhibiting autophagy in ovarian cancer via long non-coding RNA RP11-135L22.1

S.-H. Zou, X. Du, F.-D. Sun, P.-C. Wang, M. Li

Department of Pharmacy, Yantai Yuhuangding Hospital, Yantai, China. wangpengcheng1973@163.com

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• Oncology

OBJECTIVE: To observe the effect of cisplatin-induced autophagy in human ovarian cancer cell lines and explore the correlation between RP11-135L22.1 with cisplatin-induced autophagy.

MATERIALS AND METHODS: Genome-wide expression profile and chemotherapy sensitivity data of ovarian cancer were downloaded from TCGA database. It was found that the expression level of lncRNA RP11-135L22.1 differed between chemotherapy-sensitive group and insensitive group. Besides, RP11-135L22.1 expression levels were detected in 64 ovarian cancer tissues and 30 normal tissues by qRT-PCR. Relationship between RP11-135L22.1 expression levels in 64 ovarian cancer tissues and their clinicopathological characteristics were analyzed by x²-test. Cell viability was detected by CCK8 assay. Cell apoptosis and cell cycle were accessed by flow cytometry. HO8910 cells were selected for transfection of pcDNA-RP11-135L22.1, and qRT-PCR was used to evaluate RP11-135L22.1 expression in cisplatin-treated HO8910 cells. Western blot was performed to analyze the expression changes of autophagy-related proteins.

RESULTS: Genome-wide expression profile of chemotherapy-sensitive and -insensitive patients with ovarian cancer from TCGA database was analyzed by edger package. It was found that RP11-135L22.1 level in chemotherapy-sensitive group was significantly lower than that of insensitive group. QRT-PCR results confirmed that RP11-135L22.1 was lowly expressed in ovarian cancer. The overall survival of patients was positively correlated with the expression of RP11-135L22.1. Furthermore, RP11-135L22.1 was associated with FIGO stage and tumor size. Flow cytometry showed that cisplatin could induce apoptosis and arrest cell cycle in ovarian cancer cells lines. CCK8 assay showed that cisplatin decreased viability of ovarian cancer cells. For in vitro study, HO8910 cells were cultured with medium containing different concentrations of cisplatin or treated with cisplatin for different times. The results revealed that RP11-135L22.1 expression was negatively correlated with the treating time and dose of cisplatin. Western blot showed that cisplatin induced autophagy in ovarian cancer cells in a time- and dose-dependent manner. Cisplatin combined with RP11-135L22.1 can reduce autophagy, increase the apoptosis and inhibit its activity of ovarian cancer cells to a certain extent.

CONCLUSIONS: Cisplatin can induce autophagy in HO8910 ovarian cancer cells. After overexpression of RP11-135L22.1, it inhibited cisplatin-induced autophagy, thus enhancing the effect of cisplatin on ovarian cancer cells.

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