Ginkgetin induces apoptosis in ۷۸۶-O cell line via suppression of JAK۲-STAT۳ pathway

Objective(s): Renal cell carcinoma (RCC) is insensitive to conventional chemotherapy. Ginkgetin effectively treats several carcinoma cells. However, little is known about effects of Ginkgetin on RCC. In the present study, using ۷۸۶-O cells, we evaluate whether Ginkgetin exerts anticancer effects against RCC. Materials and Methods: ۷۸۶-O cells suspended in the medium containing Ginkgetin were cultured for ۲۴ hr to ۷۲ hr, and then MTT assay was used to study cytotoxic effect of Ginkgetin. Apoptosis in ۷۸۶-O was measured by an FITC Annexin apoptosis detection kit. Protein expression was detected by Western blotting. ۷۸۶-O cells with active Janus kinase ۲ (JAK۲)-Signal transducer and activator of transcription ۳ (STAT۳) were prepared by stimulant of interleukin-۶ (IL-۶), whereas ۷۸۶-O cells with deactivated STAT۳ were produced by small interfering RNA (siRNA) STAT۳. Results: Ginkgetin suppressed the growth of ۷۸۶-O in dose and time-dependent manners with IC۵۰ values of ۷.۲۳ μM. Ginkgetin induced apoptosis of ۷۸۶-O cells and increased the levels of caspase-۸, caspase-۹, and caspase-۳. Additionally, Ginkgetin treated ۷۸۶-O cells showed decreased levels of JAK۲ and phosphorylated-STAT۳ whether or not IL-۶ was pretreated. Interestingly, pretreatment of siRNA STAT۳ exerted inhibitory effects on the growth of ۷۸۶-O cells, and the observation could be further reinforced after the Ginkgetin treatment. Conclusion: Our results indicate Ginkgetin possesses obvious inhibitory effects on the proliferation of ۷۸۶-O, and this effect is probably due to its inhibition of JAK۲/STAT۳ pathway. Our findings imply Ginkgetin is a potential therapeutic medicine for RCC.

Keywords:

Apoptosis , Caspase assay , Ginkgetin , JAK۲/STAT۳ , Renal cell carcinoma