ABSTRACT
Objective: To study the effect and mechanism of thymoquinone in the growth inhibition of ovarian cancer. Methods: After ovarian cancer cells SKOV3 were treated with thymoquinone, cell growth was observed by the CCK-8 assay and apoptosis was evaluated by ELISA. ROS in SKOV3 cells was detected by fluorescent probe. The expression of Keap1 protein, nuclear Nrf2 protein, P-Akt protein, Akt protein, NQO1 protein, and GCLC protein in SKOV3 cells was analyzed by Western blotting assay. NQO1 and GCLC mRNA were analyzed by RT-PCR. SKOV3 cells were injected into nude mice to establish engrafted tumor model. Immunohistochemistry was used to detect the positive expression of NQO1, GCLC, and Nrf2 in the ovarian tumors. Results: Compared with the control group, thymoquinone significantly inhibited the proliferation of SKOV3 cells and increased the apoptosis (P < 0.05, 0.01). Thymoquinone could lessen the expression of nuclear Nrf2 protein and P-Akt protein (P < 0.05), but significantly increase the expression of Keap1 protein (P < 0.001). Protein and mRNA expression of NQO1 and GCLC in SKOV3 cells treaded by thymoquinone, were lower than those in the control group (P < 0.05, 0.01). The positive expression of NQO1, GCLC, and Nrf2 was also decreased in ovarian tumors after treatment of thymoquinone (P < 0.05, 0.01). Conclusion: Thymoquinone could inhibit the proliferation of ovarian cancer cells by inhibiting the expression of nuclear Nrf2, increasing the generation of ROS in ovarian cancer cells to promote apoptosis.