In Vivo And In Vitro Effect Of Salvia Miltrorrhiza And Its Extract In Breast Cancer

Background:Breast cancer is the most common cancer among females all over the world. Salvia Miltrorrhiza is widely used as a traditional Chinese medicine for the treatment of cardiovascular and cerebrovascular diseases. Recently, scientists demonstrated that it had anti-cancer effects in many cancer cells. Composite salviae dropping pill(CSDP) consists of Salvia Miltrorrhiza、notoginseng and borneolum.Tanshinone IIA(Ts IIA), a lipid-soluble pharmacologically active compound extracted from Salvia Miltrorrhiza, has been reported to have anti-cancer effect in many cancer cells. The aim was to assess the efficacy and safety of composite Salviae Dropping Pill in combination with chemotherapy compared to chemotherapy alone for the treatment of breast cancer(the first part), and to elucidate Ts IIA anti-breast cancer activity in vivo and in vitro.Methods:(1)Sixty patients with advanced breast cancer were randomly divided into two groups, CSDP (250mg bid dl-21)combined EC regimen (EPI75mg/m2dl,CTX600mg/m2dl) and EC regimen alone, and each group had30cases. The study was to assess the efficacy、safety and quality of life in the two groups.(2)The in vitro effects of Ts IIA in the cell proliferation and invasion were examined by CCK8and transwell assay. Apoptotic signaling cascades were explored by western blotting analysis.Results:(1)There is not significant difference between the two groups in objective response rate (CR+PR), but the CDSP group had good clinical benefit response rate (CR+PR+SD)(93.3%vs73.3%p<0.05). CDSP group showed a tendency in prolonging TTP, but no significant difference was found(8.8vs5.7m,95%CI0.95-2.12, P=0.210). The quality of life was also better in the CDSP group. While the incidence of cardiotoxicity events in CDSP group was lower than in EC group.(2)In vitro studies showed that Ts IIA inhibited proliferation of the two breast cancer cells in a dose-dependent and time-dependent manner, and the Western blotting data indicated it could also induce apoptosis depending on activating Caspse-9and caspase-3. Results of transwell assay showed that Ts IIA could significantly decrease invasion capability of MDA-MB231(P<0.05).Conclusion:(1) CSDP combined with EC regimen gives a satisfactory clinical benefit response rate, improving the life quality, reducing EPI-inducing cardiotoxcity of patients with advanced breast cancer in clinical practice and also have a tendency in prolonging TTP.(2)Tanshione Ⅱ A could inhibit the proliferation, induce apoptosis by activating caspase-9and caspase-3of breast cancer cell in vi t ro. These results also suggest that Ts IIA could inhibit invasion of MDA-MB231cells significantly. Therefore, Salvia Miltrorrhiza and its extract merits therapeutic potential for breast cancer treatment.