Combination of SB431542, CHIR99021 and PD0325901 has a synergic effect on abrogating valproic acid ‑induced epithelial‑mesenchymal transition and stemness in HeLa, 5637 and SCC‑15 cells.

Combination of SB431542, CHIR99021 and PD0325901 has a synergic effect on abrogating valproic acid‑induced epithelial‑mesenchymal transition and stemness in HeLa, 5637 and SCC‑15 cells. Oncol Rep. 2019 Apr 01;: Authors: Zhang Y, Zhang Y, Li M, Meng F, Yu Z, Chen Y, Cui G Abstract Epithelial‑mesenchymal transition (EMT) plays an important role in cancer progression, metastasis and drug resistance, and recent studies have revealed that neoplastic epithelial cells regain the stem cell state through EMT. Single‑agent targeted cancer therapy frequently fails due to acquired drug resistance. Therefore, multi‑agent targeted therapy exhibits advantages in fighting cancer cells. In the present study, small molecule inhibitors SB431542 (ALK inhibitor), CHIR99021 (GSK3 pathway inhibitor), PD0325901 (MEK/ERK inhibitor) and valproic acid (VPA; HDAC inhibitor) were applied individually or in combination to HeLa uterine cervix carcinoma cells, 5637 bladder cancer cells and SCC‑15 squamous cell carcinoma cells to clarify their potential effects on cancer cells. Cell morphological alterations, pluripotency and EMT‑related gene expression, cell growth rate, cell migration, signal transduction, cell cycle arrest, CD24‑/CD44+ cell percentage, and in vivo tumor clump formation were evaluated. The results of the present study revealed that VPA treatment induced EMT morphology, upregulated the expression of pluripotency and EMT‑relate...
Source: Oncology Reports - Category: Cancer & Oncology Tags: Oncol Rep Source Type: research