Thermo-chemotherapy Inhibits the Proliferation and Metastasis of Gastric Cancer Cells Via Suppression of EIF5A2 Expression

Overview

Journal Onco Targets Ther

Publisher Dove Medical Press

Specialty Oncology

Date 2019 Sep 10

PMID 31496731

Citations 5

Authors

Ming-Chen Ba

Zheng Ba

Shu-Zhong Cui

Yuan-Feng Gong

Cheng Chen

Kun-Peng Lin

Yin-Bing Wu

Yi-Nuo Tu

Affiliations

Soon will be listed here.

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.

Citing Articles

Iron oxide nanoparticles coated with bioactive materials: a viable theragnostic strategy to improve osteosarcoma treatment.

Benjamin A, Nayak S Discov Nano. 2025; 20(1):18.

PMID: 39883285 PMC: 11782756. DOI: 10.1186/s11671-024-04163-w.

The therapeutic efficacy of different configuration nano-polydopamine drug carrier systems with photothermal synergy against head and neck squamous cell carcinoma.

Guo Y, Li B, Xie H, Wu C, Wang G, Yao K Regen Biomater. 2024; 11:rbae073.

PMID: 39027362 PMC: 11256922. DOI: 10.1093/rb/rbae073.

Multi-Omics Analysis of the Effects of Smoking on Human Tumors.

Wang R, Li S, Wen W, Zhang J Front Mol Biosci. 2021; 8:704910.

PMID: 34796198 PMC: 8592943. DOI: 10.3389/fmolb.2021.704910.

Knockdown of lncRNA ZNRD1-AS1 suppresses gastric cancer cell proliferation and metastasis by targeting the miR-9-5p/HSP90AA1 axis.

Ba M, Ba Z, Gong Y, Lin K, Wu Y, Tu Y Aging (Albany NY). 2021; 13(13):17285-17301.

PMID: 34226297 PMC: 8312431. DOI: 10.18632/aging.203209.

Establishment of a 5-gene risk model related to regulatory T cells for predicting gastric cancer prognosis.

Hu G, Sun N, Jiang J, Chen X Cancer Cell Int. 2020; 20:433.

PMID: 32908454 PMC: 7470613. DOI: 10.1186/s12935-020-01502-6.

References

Jenkins Z, Haag P, Johansson H . Human eIF5A2 on chromosome 3q25-q27 is a phylogenetically conserved vertebrate variant of eukaryotic translation initiation factor 5A with tissue-specific expression. Genomics. 2001; 71(1):101-9. DOI: 10.1006/geno.2000.6418. View

Xie D, Ma N, Pan Z, Wu H, Liu Y, Wu G . Overexpression of EIF-5A2 is associated with metastasis of human colorectal carcinoma. Hum Pathol. 2007; 39(1):80-6. DOI: 10.1016/j.humpath.2007.05.011. View

Calcagno D, Leal M, Assumpcao P, Smith M, Burbano R . MYC and gastric adenocarcinoma carcinogenesis. World J Gastroenterol. 2008; 14(39):5962-8. PMC: 2760197. DOI: 10.3748/wjg.14.5962. View

Yang G, Xie D, Liu J, Luo J, Li L, Hua W . Expression and amplification of eIF-5A2 in human epithelial ovarian tumors and overexpression of EIF-5A2 is a new independent predictor of outcome in patients with ovarian carcinoma. Gynecol Oncol. 2008; 112(2):314-8. DOI: 10.1016/j.ygyno.2008.10.024. View

He L, Zhao H, Li B, Liu Y, Liu M, Guan X . Overexpression of eIF5A-2 is an adverse prognostic marker of survival in stage I non-small cell lung cancer patients. Int J Cancer. 2010; 129(1):143-50. DOI: 10.1002/ijc.25669. View

Zhu W, Cai M, Tong Z, Dong S, Mai S, Liao Y . Overexpression of EIF5A2 promotes colorectal carcinoma cell aggressiveness by upregulating MTA1 through C-myc to induce epithelial-mesenchymaltransition. Gut. 2011; 61(4):562-75. DOI: 10.1136/gutjnl-2011-300207. View

Xiao F, Liu B, Zhu Q . c-Jun N-terminal kinase is required for thermotherapy-induced apoptosis in human gastric cancer cells. World J Gastroenterol. 2013; 18(48):7348-56. PMC: 3544041. DOI: 10.3748/wjg.v18.i48.7348. View

Tang Y, McGoron A . Increasing the rate of heating: a potential therapeutic approach for achieving synergistic tumour killing in combined hyperthermia and chemotherapy. Int J Hyperthermia. 2013; 29(2):145-55. DOI: 10.3109/02656736.2012.760757. View

Wang F, Guan X, Xie D . Roles of eukaryotic initiation factor 5A2 in human cancer. Int J Biol Sci. 2013; 9(10):1013-20. PMC: 3831114. DOI: 10.7150/ijbs.7191. View

10.

Xu G, Yu H, Shi X, Sun L, Zhou Q, Zheng D . Cisplatin sensitivity is enhanced in non-small cell lung cancer cells by regulating epithelial-mesenchymal transition through inhibition of eukaryotic translation initiation factor 5A2. BMC Pulm Med. 2014; 14:174. PMC: 4232729. DOI: 10.1186/1471-2466-14-174. View

11.

Torre L, Bray F, Siegel R, Ferlay J, Lortet-Tieulent J, Jemal A . Global cancer statistics, 2012. CA Cancer J Clin. 2015; 65(2):87-108. DOI: 10.3322/caac.21262. View

12.

Meng Q, Kang W, Yu J, Liu Y, Ma Z, Zhou L . Overexpression of eukaryotic translation initiation factor 5A2 (EIF5A2) correlates with cell aggressiveness and poor survival in gastric cancer. PLoS One. 2015; 10(3):e0119229. PMC: 4368542. DOI: 10.1371/journal.pone.0119229. View

13.

Mathews M, Hershey J . The translation factor eIF5A and human cancer. Biochim Biophys Acta. 2015; 1849(7):836-44. PMC: 4732523. DOI: 10.1016/j.bbagrm.2015.05.002. View

14.

Thrumurthy S, Chaudry M, Chau I, Allum W . Does surgery have a role in managing incurable gastric cancer?. Nat Rev Clin Oncol. 2015; 12(11):676-82. DOI: 10.1038/nrclinonc.2015.132. View

15.

Liu Y, Liu R, Fu P, Du F, Hong Y, Yao M . N1-Guanyl-1,7-Diaminoheptane Sensitizes Estrogen Receptor Negative Breast Cancer Cells to Doxorubicin by Preventing Epithelial-Mesenchymal Transition through Inhibition of Eukaryotic Translation Initiation Factor 5A2 Activation. Cell Physiol Biochem. 2015; 36(6):2494-503. DOI: 10.1159/000430209. View

16.

Yang Q, Ye Z, Zhang Q, Zhao Z, Yuan H . Expression of eukaryotic translation initiation factor 5A-2 (eIF5A-2) associated with poor survival in gastric cancer. Tumour Biol. 2015; 37(1):1189-95. DOI: 10.1007/s13277-015-3894-0. View

17.

Liu R, Lv Y, Tang Y, Wang Y, Chen X, Zheng X . Eukaryotic translation initiation factor 5A2 regulates the migration and invasion of hepatocellular carcinoma cells via pathways involving reactive oxygen species. Oncotarget. 2016; 7(17):24348-60. PMC: 5029706. DOI: 10.18632/oncotarget.8324. View

18.

Huang P, Zeng T, Ban X, Li M, Zhang B, Zhu Y . Expression of EIF5A2 associates with poor survival of nasopharyngeal carcinoma patients treated with induction chemotherapy. BMC Cancer. 2016; 16:669. PMC: 4994420. DOI: 10.1186/s12885-016-2714-2. View

19.

Ramanan M, Pilli V, Aradhyam G, Doble M . Transcriptional regulation of microsomal prostaglandin E synthase 1 by the proto-oncogene, c-myc, in the pathogenesis of inflammation and cancer. Biochem Biophys Res Commun. 2016; 482(4):556-562. DOI: 10.1016/j.bbrc.2016.11.073. View

20.

Yeung K, Yang J . Epithelial-mesenchymal transition in tumor metastasis. Mol Oncol. 2017; 11(1):28-39. PMC: 5242415. DOI: 10.1002/1878-0261.12017. View