Effect Of Thymoquinone Combined With Doxorubicin On The Growth Inhibition Of Osteosarcoma In Vitro And In Vivo

Objective:To investigate the effect of thymoquinone on the sensitization of osteosarcoma to doxorubicin as well as its mechanisam.Methods:After human osteosarcoma SaOS-2cells were treated with thymoquinone, doxorubicin and thymoquinone combined doxorubicin, the cellular proliferation was detected by Cell Counting Kit-8(CCK-8) assay. The flow cytometry was accustomed to determine death in SaOS-2cells. Western blotting was accustomed to detect the protein utterance of bcl-2and Bax. In vivo antitumor effects of thymoquinone and doxorubicin were assessed using SaOS-2xenograft in BALB/c nude mice model. Immunohistochemistry was accustomed to detect the active utterance of Ki-67, Bcl-2and Bax in the xenograft tumors.Results:The viability rates of thymoquinone, doxorubicin and thymoinone+doxorubicin on SaOS-2cells were (78.94±8.75)%(67.41±5.26)%and (38.81±3.58)%, respectively. The rates of apoptotic cell of thymoquinone, doxorubicin and thymoinone combined doxorubicin were (8.85±1.25)%,(11.26±2.51)%and (7.15±3.25)%, respectively. The expression of Bax and Bcl-2were regulated, separately in SaOS-2cells after treatment of thymoquinone plus doxorubicin. Thymoquinone or doxorubicin alone caused37.51%and48.37%reduction in tumor weight, respectively, but administration of thymoquinone combined doxorubicin caused66.85%reduction in tumor weight. Compared with the control and doxorubicin alone, treated with thymoquinone combined with doxorubicin significantly increased the expression of Bax in tumor tissues, but the positive expression of Ki-67and Bcl-2were decreased.Conclusion: Thymoquinone could potentiate the growth inhibition of osteosarcoma induced by doxorubicin both in vitro and in vivo, which may be related to up-regulation of Bax and down-regulation of Bcl-2.