Tanshinone I attenuates proliferation and chemoresistance of cervical cancer in a KRAS-dependent manner

Chemoresistance is a common occurrence during advanced or recurrent cervical cancer therapy when treated by conventional treatment, platinum-based chemotherapy. This study aimed to investigate the effect and underlying mechanism of tanshinone I on attenuating proliferation and chemoresistance of cervical cancer cells. In cervical cancer cells, cell proliferation was examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), cell count, and soft-agar colony-formation assay. rVista analysis and luciferase reporter assay were used to explore the upstream regulator of KRAS, and the expression levels of key genes were also detected. Western blot analysis showed that tanshinone I significantly suppressed KRAS expression and inhibited AKT phosphorylation. rVista analysis and luciferase reporter assay demonstrated that ELK1 can binds directly to KRAS promoter and positively regulates KRAS expression. MTT assay showed that KRAS or ELK1 overexpression significantly attenuated the suppressive effects of tanshinone I on HeLa cells proliferation. In addition, tanshinone I recovered the cisplatin sensitivity of HeLa CR cells, whereas KRAS or ELK1 overexpression significantly inhibited this phenomenon. Our results suggested that tanshinone I had anticancer effects on cervical cancer cells via inhibiting ELK1 and downregulating KRAS-AKT axis, which subsequently suppressed the proliferation and cisplatin resistance of cervical cancer cells.