Tumor-treating fields in combination with sorafenib curtails the growth of colorectal carcinoma by inactivating AKT/STAT3 signaling

肿瘤治疗场与索拉非尼联合使用可通过抑制 AKT/STAT3 信号来抑制结直肠癌的生长

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作者:Eun Ho Kim, Won Seok Lee, Hoon-Kyu Oh

Background

Tumor-treating fields (TTFields) have been extensively used to treat various cancers as well as glioblastoma multiforme (GBM), owing to their antimitotic effects. Furthermore, sorafenib is also extensively used to treat hepatocellular carcinoma (HCC) and renal cell carcinoma (RCC) and is under phase II/III clinical trials for other solid tumors. Hence, this investigation aimed to assess the efficacy of combination therapy with TTFields and sorafenib for colorectal carcinoma (CRC).

Conclusions

Thus, combination treatment with TTFields and sorafenib is clinically applicable for treating metastatic CRC, although safety examination in patients with CRC will required to be achieved before this protocol can be implemented clinically for TTFields-sensitizer.

Methods

Human CRC HCT116 and SW480 cells were subjected to cell viability assay, followed by the assessment of their cell death using fluorescence-activated cell sorting (FACS) analysis. Furthermore, the expression of proteins involved in AKT/STAT3 signaling and apoptosis was assessed via western blotting.

Results

Combination treatment inhibited cell proliferation and induced apoptosis via Reactive oxygen species (ROS) generation, evident from caspase-3 cleavage in CRC cells and suppressed the AKT/STAT3 signaling pathway, as evident from downregulation of BCL-2 after post-treatment. The present results indicate that combination treatment with TTFields and sorafenib inactivates AKT/STAT3 signaling pathway, thus altering the expression of BCL-2, thus inducing apoptosis and inhibiting the growth of CRC cells. Conclusions: Thus, combination treatment with TTFields and sorafenib is clinically applicable for treating metastatic CRC, although safety examination in patients with CRC will required to be achieved before this protocol can be implemented clinically for TTFields-sensitizer.

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