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Effects and mechanisms of shikonin on the radiation sensitization of human ovarian cancer cell line SKOV-3
Abstract:Objective: To investigate the radiosensitizing?effect and the underlying mechanism of shikonin on the human ovarian cancer cell line SKOV-3. Methods: The viability of SKOV-3 cells after treating with different concentrations (0,5,10,20,40,8 0 and 120 μg/mL) of shikonin was measured by MTT assay; The survival rate of SKOV-3 cells after treating with different doses(0,2,4,6 and 8 Gy) of x-ray radiotherapy was testet by clone forming assay.The SKOV-3 cells were divided into 4 groups: the Control group (Control group), the Shk group (8μg/mL Shk treatment), the 8 Gy group (8 Gy X-ray radiotherapy treatment) and the Shk + 8 Gy group (8 Gy μg/mL Shk treatment for 48 hours, followed by 8 Gy X-ray radiotherapy treatment). The cell cycle was examined by PI staining using flow cytometry and the phosphorylation of PI3K and AKT levels were analyzed by western blotting in each group. Results: In the ranged of 0-80μg/mL, shikonin decreased SKOV-3 cell viability in a concentration-dependent manner(P<0.05). The value of IC50 was 38.54±0.57 μg/mL. Compared with radiotherapy alone, the survival curve was markedly shit to the left after shikonin combined radiotherapy(P<0.05). The value of radiotherapy sensitization ratio (SER) was 1.45±0.05. Moreover, Compared with 8 Gy alone group, the percentage of G2/M phase and the phosphorylation levels of PI3K and AKT were decreased in Shk+8 Gy group(P<0.05). Conclusion: Shikonin could increase the radiosensitivity of SKOV-3, and the mechanism may be related to attenuat radiation-induced the G2/M phase arrest and inhibition of PI3K/AKT signaling pathway.
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