Figure 7.

CXCR4 Promotes Cisplatin Resistance of OC Cells through Suppressing the let-7a/BCL-XL/S Axis

(A) Relative let-7a expression levels in OC tissues and adjacent non-cancerous ovarian tissues. Expressional changes of let-7a in OC tissues were analyzed by qRT-PCR. (B) Negative correlation of let-7a with CXCR4 expression in OC tissues. (C) Relative let-7a expression in SKOV3, Caov3, OVCAR3, A2780, and CAV644 cells. Its expression in HOSE cells was detected as the control. (D and E) Silencing and elevation of CXCR4 expression in SKOV3 and Caov3 cells with shCXCR4 and pcDNA3.1-CXCR4 plasmids, respectively. Expression levels of CXCR4 in SKOV3 and Caov3 cells were detected by qRT-PCR (D) and western blotting (E). (F) Relative expression of let-7a in SKOV3 and Caov3 cells with silenced or elevated CXCR4 expression by qRT-PCR. (G) Influences of shCXCR4 and let-7a inhibitor on cisplatin resistance of SKOV3 and Caov3 cells. Cell viabilities were detected by the CCK-8 method under treatments with 2, 4, 6, 8, or 10 μM cisplatin, and the resistances were assessed by the IC₅₀ values. (H) Effects of shCXCR4 and let-7a inhibitor on cisplatin-induced SKOV3 and Caov3 cell apoptosis. Flow cytometry was performed to detect cell apoptosis. (I) Abundances of BCL-XL/S proteins in SKOV3 and Caov3 cells transfected with shCXCR4 and let-7a inhibitor. Protein levels were analyzed by western blotting. (J) The binding of let-7a with BCL-XL/S gene sequences predicted by informatics (top) and confirmed by dual-luciferase reporter assay (bottom). NC, negative control; CXCR4, chemokine receptor 4; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; IC₅₀, half maximal inhibitory concentration; ∗p < 0.05, ∗∗p < 0.01, and ∗∗∗p < 0.001.