Overexpression of GATA5 Stimulates Paclitaxel to Inhibit Malignant Behaviors of Hepatocellular Carcinoma Cells (Pages: 89-100)


Haipeng Feng , Bo Lin , Yifei Zheng , Junnv Xu , Ying Zhou , Kun Liu , Mingyue Zhu , Mengsen Li *,

Objective

Explore overexpression of GATA5 influence the role of Paclitaxel on inhibiting the growth of hepatocellular carcinoma (HCC) cells.

MaterialsAndMethods

HCC cell lines, HLE, Bel 7402and PLC/PRF/5 were treated with different concentration of paclitaxel(5-20g/ml) for24hours; HLE cells were transfected with GATA5-siRNAvector, Bel 7402 and PLC/PRF/5 cells were transfected with GATA5 overexpression vector for 24 hours followed treatment of Paclitaxel(10g/ml) for 24 hours, then MTT assay was applied to detect growth of HCC cells; soft agar cultured was used to analyze the formation of colony; the apoptosis of HCC cells were detected by Flow cytometry; the migration of HCC cells was observed by migration assays; Western blotting and laser confocal microscopy were utilized to detected the expression and location of proteins.

Results

Inhibited the expression of GATA5 reduced the sensitivity of HLE cells to paclitaxel, and overexpression of GATA5 increased the sensitivity of BEL7402 cells and PLC/PRF/5 cells to paclitaxel. Overexpression ofGATA5 played a role in stimulating paclitaxel to inhibit cell growth, colony formation, and migration, as well as enhance apoptosis in HCC cells. Overexpression of GATA5 also promoted paclitaxel to inhibit the expression of reprogramming genes, such as Nanog, EpCAM, C-myc, and Sox2 in Bel 7402 and PLC/PRF/5 cells. Inhibited expression of GATA5 was able to enhance the expression of CD44 and CD133, in HLE cells. The overexpression of GATA5 not only alone but also synergized with paclitaxel to decrease the expression of CD44 and CD133 in Bel7402 cellsor PLC/PRF/5 cells.

Conclusion

Overexpression of GATA5 played a role in enhancing paclitaxel to inhibit the malignant behaviors of HCC cells, the role mechanism maybe involve in suppressing the expression of reprogramming genes and stemness markers, GATA5 is a novel biotarget for applying paclitaxel to therapy of patients with HCC.