Paclitaxel inhibits the progression of cervical cancer by inhibiting autophagy via IncRNARP11-381N20.2

OBJECTIVE: To observe the effect of paclitaxel on the autophagy of human cervical cancer cell lines by the expression regulation of IncRNARP11-381N20.2 as well as to explore the interaction and relationship between autophagy, proliferation, and apoptosis of cervical cancer cells. MATERIALS AND METHODS: Genome-wide expression profiles of tumors and their susceptibility to drugs were downloaded through TCGA database to find differentially expressed lncRNA RP11-381N20.2 in chemosensitive sensitive and insensitive groups. Expression of RP11-381N20.2 in 60 cervical cancer tissues and 30 normal tissues was detected by qRT-PCR. The relationship between the expression of RP11-381N20.2 and the clinicopathological parameters of lung cancer was statistically analyzed. The recombinant plasmid pcDNA-RP11-381N20.2 and pcDNA-NC of RP11-381N20.2 were transfected into SiHa cells by lipofectamine, respectively. The autophagy and phenotypic effects were observed. Cell proliferation was determined by colony formation assay. Apoptosis was detected by flow cytometry. Western blot was conducted to detect expressions of autophagy-related proteins. RESULTS: Genome-wide expression profiles of chemotherapy-sensitive and insensitive data in patients with cervical cancer in TCGA database were analyzed by edger package, results showed that the expression of lncRNA RP11381N20.2 was significantly lower in the chemotherapy- insensitive group. qRT-PCR results showed that the expression of RP11-381N20.2 in cervical cancer was decreased, and the total survival time of patients was positively correlated with the expression of RP11-381N20.2. RP11381N20.2 was associated with TNM (tumor node metastasis) staging and tumor size. Biological functions of SiHa cells showed that the expression of RP11-381N20.2 was negatively correlated with the treatment time and dose of paclitaxel. Colony formation assay showed that paclitaxel could inhibit the proliferation of cervical cancer cells in a dose-dependent manner. Flow cytome-try showed that paclitaxel induced apoptosis of cervical cancer cells, which was more promoted after combination with RP11-381N20.2. Western blot results suggested that paclitaxel could induce autophagy in cervical cancer cells in a time-and dose-dependent manners. Paclitaxel combined with RP11-381N20.2 could significantly increase apoptosis of cervical cancer cells. CONCLUSIONS: During the killing process of paclitaxel on cervical cancer SiHa cells, cell autophagy would affect the efficacy, after overexpression of RP11-381N20.2 in SiHa cells, autophagy induced by paclitaxel was inhibited, thereby enhancing the killing effect of paclitaxel on tumor cells.