Tanshinone IIA inhibits proliferation and migration by downregulation of the PI3K/Akt pathway in small cell lung cancer cells

Abstract

AbstractBackground Small cell lung cancer (SCLC) is the most malignant type of lung cancer. Due to the high rates of metastasis and drug resistance, effective therapeutic strategies are lacking. Tanshinone IIA (Tan IIA) has been reported to exhibit anti-tumor activity. Therefore, in this study, we investigated the ability of Tan IIA to inhibit the metastasis and proliferation of SCLC and the underlying mechanism. Methods H1688 cells were treated in vitro with Tan IIA (0, 1, 2 and 4 µM) and LY294002 (10 µM) for 24, 48, 72 hours. H1688 cell migration was evaluated in wound healing and transwell migration assays. Expression of genes was evaluated by RNA-sequencing. BALB/c nude mice were injected with H1688 cells and treated with Tan IIA group (10 mg/kg/day) or a control. Expression of E-cadherin, vimentin and PI3K/Akt signaling pathway proteins in tumors and in H1688 was investigated by immunohistochemical analysis and western blot, respectively. Results Tan IIA inhibited H1688 cell proliferation without inducing apoptosis and suppressed H1688 cell migration. E-cadherin expression was increased, while vimentin expression was reduced after administration of Tan IIA. The analysis of RNA-sequencing showed that some genes associated with PI3K/Akt signaling pathway were altered by Tan IIA treatment. Furthermore, western blot detected the expression of PI3K and p-Akt was also reduced by Tan IIA treatment. In vivo, Tan IIA inhibited tumor growth. Furthermore, Tan IIA increased tumoral expression of E-cadherin accompanied by downregulation of PI3K and p-Akt. Conclusion Tan IIA suppresses SCLC proliferation and metastasis by inhibiting the PI3K/Akt signaling pathway, thus indicating the potential of Tan IIA as a new and relatively safe drug candidate for the treatment of SCLC.