Baicalein improves the chemoresistance of ovarian cancer through regulation of CirSLC7A6

Abstract

Purpose: The present study aimed to investigate whether baicalein improves the sensitivity of resistant ovarian cancer cells to cisplatin.

Methods: Transcriptomic sequencing and bioinformatics analysis were used to screen differentially expressed CirSLC7A6 in A2780 and A2780/CDDP cells. RT-qPCR was performed to examine the expression levels of CirSLC7A6, miR-2682-5p, and SLC7A6. Cell proliferation and apoptosis were examined using a Cell Counting Kit-8 assay and flow cytometry, and cell migration and invasion were analyzed using wound healing and Transwell assays. Cell suspensions were inoculated into the subcutaneous tissues of the bilateral interscapular region of nude mice. Saline, cisplatin, baicalein and cisplatin plus baicalein were intraperitoneally injected to observe the effects on tumor growth. Toxicity analyses in the liver and kidney were performed using H&E staining. RT-qPCR and immunohistochemistry were used to detect the expression of CirSLC7A6, miR-2682-5p, and SLC7A6 in tumor tissues, and western blot analysis was carried out to measure protein expression levels.

Results: CirSLC7A6 was markedly upregulated in A2780/CDDP cells compared with the A2780 cells. CirSLC7A6 knockdown notably increased the expression of miR-2682-5p and decreased SLC7A6 expression. The rates of inhibition and apoptosis in the group treated with a combination of cisplatin and baicalein were significantly higher than those of the cisplatin and baicalein groups of A2780/CDDP shCirSLC7A6 cells. In A2780/CDDP shCirSLC7A6 cells, migration and invasion were significantly higher in the cisplatin and baicalein groups, compared with the combined treatment group. In the A2780/CDDP shCirSLC7A6 cell xenograft, the tumor weight of the combined treatment group was significantly lower than that of the cisplatin and baicalein groups. In addition, the combination of cisplatin and baicalein did not induce higher levels of toxicity in the liver or kidney. Baicalein alone and in combination with cisplatin notably reduced the expression of CirSLC7A6 and SLC7A6, and increased the expression of miR-2682-5p in the A2780/CDDP shCirSLC7A6 cell xenograft. In A2780/CDDP shCirSLC7A6 cells, the expression levels of P-Akt, P-mTOR, P-Erk, Bcl-2 and MMP2 were lower in the combined treatment group than in the control group.

Conclusions: Treatment with baicalein improved the sensitivity of ovarian cancer cells to cisplatin and inhibited cell proliferation, metastasis and tumor growth.

Keywords: Baicalein; Chemoresistance; CirSLC7A6; Ovarian cancer; SLC7A6.