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. 2019 Aug 9:12:6275-6284.
doi: 10.2147/OTT.S215590. eCollection 2019.

Thermo-chemotherapy inhibits the proliferation and metastasis of gastric cancer cells via suppression of EIF5A2 expression

Ming-Chen Ba #  1 , Zheng Ba #  2 , Shu-Zhong Cui  1 , Yuan-Feng Gong  1 , Cheng Chen  1 , Kun-Peng Lin  1 , Yin-Bing Wu  1 , Yi-Nuo Tu  1
Affiliations

Thermo-chemotherapy inhibits the proliferation and metastasis of gastric cancer cells via suppression of EIF5A2 expression

Ming-Chen Ba et al. Onco Targets Ther. .

Abstract

Purpose: Thermo-chemotherapy (TCT) is a new approach for the treatment of cancer that combines chemotherapy with thermotherapy. In the present study, we investigated the relationship between eukaryotic translation initiation factor 5A2 (EIF5A2) and TCT sensitivity in gastric cancer (GC) to further illuminate the molecular mechanism underlying the effect of TCT on GC.

Methods: A TCT cell model was constructed, and EIF5A2 was silenced or overexpressed by infection with a lentivirus expressing either EIF5A2 or EIF5A2 shRNA. Then, RT-qPCR, Western blotting, and immunohistochemistry assays were performed to evaluate the changes in the expression levels of EIF5A2, c-myc, vimentin, and E-cadherin. Cell proliferation and xenograft assays were conducted to evaluate the effect on cell proliferation. Finally, wound-healing and Transwell invasion assays were performed to evaluate the effects on migration and invasion.

Results: TCT reduced EIF5A2 expression at both the mRNA and protein levels. It also inhibited cell proliferation, migration, and invasion, downregulated the expression of c-myc and vimentin, and increased the expression of E-cadherin in both MKN28 and MKN45 cells. Silencing of EIF5A2 enhanced the above effects of TCT on MKN28 and MKN45 cells, while overexpression of EIF5A2 had the opposite effects. In addition, EIF5A2 overexpression weakened the inhibitory effect of TCT on tumor growth in vivo as well as the effects on c-myc, vimentin, and E-cadherin.

Conclusion: TCT inhibits GC cell proliferation and metastasis by suppressing EIF5A2 expression. Our results provide new insights into our understanding of the molecular mechanism underlying the effects of TCT in GC.

Keywords: EIF5A2; epithelial-mesenchymal transition; gastric cancer; proliferation; thermo-chemotherapy.

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Conflict of interest statement

The authors have no conflicts of interest pertaining to this work.

Figures

Figure 1
Figure 1
The expression levels of EIF5A2 in MKN28 and MKN45 cells subjected to thermo-chemotherapy (TCT). (A) The mRNA expression of EIF5A2 in MKN28 and MKN45 cells subjected to TCT was measured using RT-qPCR. (B) The protein expression of EIF5A2 in MKN28 and MKN45 cells subjected to TCT was analyzed using Western blotting. (***P<0.001).
Figure 2
Figure 2
The effect of EIF5A2 expression and thermo-chemotherapy (TCT) on the proliferation of MKN28 and MKN45 cells was measured using the CCK-8 assay. *P<0.05,***P<0.001.
Figure 3
Figure 3
The effect of EIF5A2 expression and thermo-chemotherapy (TCT) on the migration of MKN28 and MKN45 cells was measured using a wound healing assay. The upper part is the representive images, and lower part is the statistical results of wound closure. ***P<0.001.
Figure 4
Figure 4
The effect of EIF5A2 expression and thermo-chemotherapy (TCT) on the proliferation of MKN28 and MKN45 cells was measured using a Transwell cell invasion assay. The upper part is the representive images, and the lower part is the statistical results of invasion cells per field. ***P<0.001.
Figure 5
Figure 5
The effect of EIF5A2 expression and thermo-chemotherapy (TCT) on the mRNA and protein expression levels of c-myc, vimentin, and E-cadherin in MKN28 and MKN45 cells. (A–C) The mRNA expression levels of c-myc, vimentin, and E-cadherin in MKN28 and MKN45 cells subjected to TCT were measured using RT-qPCR. (D) The protein expression levels of c-myc, vimentin, and E-cadherin in MKN28 and MKN45 cells subjected to TCT were measured using Western blotting. ***P<0.001.
Figure 6
Figure 6
The effect of EIF5A2 overexpression and thermo-chemotherapy (TCT) on tumor growth in vivo. (A) Solid tumors were removed from mouse subcutaneous tissue. (B) The mean volume of ov-EIF5A2 or ov-NC cell-derived xenograft tumors generated from MKN28 and MKN45 cells subjected to TCT. ***P<0.001.
Figure 7
Figure 7
Representative immunohistochemical images showing the expression levels of EIF5A2, c-myc, vimentin, and E-cadherin in ov-EIF5A2 or ov-NC cell-derived tumor cells of MKN28 and MKN45 subjected to thermo-chemotherapy (TCT).
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