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

Abstract

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.

Circular RNA hsa_circ_0000515 acts as a miR-326 sponge to promote cervical cancer progression through up-regulation of ELK1

“…ELK1 triggers a proto-oncogene c-Fos, downstream target, by which ELK1 stimulates the growth of bladder cancer cells [36]. In line with our data that ELK1 over-expression promoted cervical cancer development, ELK1 is also able to inhibit the suppressive effects of Tanshinone I on proliferation of HeLa cells [37]. Inhibition of ELK1 is capable of suppressing thyroid cancer progression [38].…”

The Anticancer Properties of Tanshinones and the Pharmacological Effects of Their Active Ingredients

“…The expression of p-AKT and kainate receptors (KARS) was markedly suppressed by Tan I treatment. In contrast, overexpression of KRAS or ETS-like 1 transcription factor (ELK1) markedly impaired the suppression of Tan I on HeLa cells (Dun and Gao, 2018). In the research of Li et al, Tan I showed the most potent effect on the proliferation of lung cancer cells compared with CT and Tan IIA.…”

Recurrence Pattern of Cervical Cancer Based on the Platinum Sensitivity Concept: A Multi-Institutional Study from the FRANCOGYN Group

“…The prognostic impact of platinum status, and the current absence of an effective therapeutic alternative, underline the need for a better understanding of the chemoresistance mechanism in CC patients. Several studies have focused on various molecular and genetic factors such as microRNAs [25], tanshinone I [26], enhancer of zeste homolog 2 [27], and polymorphisms in the PI3K/Akt pathway [28] among others, with promising results.…”