Background: Paclitaxel is a widely used clinical first line chemotherapy drug for ovarian carcinoma. Tanshinone I (Tan-I) is one of the vital fat-soluble components, which derived from Chinese herbal medicine, Salvia miltiorrhiza Bunge. Herein, we evaluated whether Tan-I could enhance the efficacy of ovarian cancer to chemotherapy of Paclitaxel.
Methods: Ovarian cancer cells A2780 and ID-8 were exposed with Tan-I (4.8 µg/mL), Paclitaxel (0.1 µg/mL), or Tan-I combination with Paclitaxel for 24 hours. The cell proliferation was analyzed by CCK8 and EdU staining. Cell apoptosis was analyzed by the TUNEL assay and flow cytometry. The protein levels were determined by western blot. Cell migration was analyzed by Transwell and wound healing. Cell senescence was analyzed by senescence-associated b-galactosidase staining. Antitumor activity was analyzed by a subcutaneous tumor xenograft model of human ovarian cancer in nude mice. The protein expression and apoptosis level of tumor tissues were analyzed by immunohistochemistry and TUNEL staining.
Results: Tan-I treatment significantly elevated the Paclitaxel-cause reduction of A2780 and ID-8 cell proliferation and cell migration. Tan-I combination with Paclitaxel promotes apoptosis of cancer cells by promoting Bax expression and Bcl-2 expression. Besides, Tan-I treatment can notably increase Paclitaxel-inducing cell senescence by promoting DNA damage and senescence-associated proteins such as p21 and p16. Furthermore, the result of the transplanted tumor model indicated that Tan-I combination with Paclitaxel could inhibit tumor growth in vivo by inhibiting cell proliferation and inducing cell apoptosis.
Conclusions: Natural compound Tan-I enhances the efficacy of ovarian cancer to Paclitaxel chemotherapy. The results will help to supply the potential clinical use of ovarian carcinoma cells.
Keywords: Paclitaxel; Tanshinone I (Tan-I); apoptosis; cell migration; cell senescence; ovarian carcinoma; tumor growth.
2020 Annals of Translational Medicine. All rights reserved.