Oct-4 induces cisplatin resistance and tumor stem cell-like properties in endometrial carcinoma cells

Ta-Chin Lin; Kai-Hung Wang; Kuo-Hsiang Chuang; An-Pei Kao; Tsung-Cheng Kuo

doi:10.1016/j.tjog.2022.08.014

Oct-4 induces cisplatin resistance and tumor stem cell-like properties in endometrial carcinoma cells

Taiwan J Obstet Gynecol. 2023 Jan;62(1):16-21. doi: 10.1016/j.tjog.2022.08.014.

Authors

Ta-Chin Lin¹, Kai-Hung Wang², Kuo-Hsiang Chuang³, An-Pei Kao⁴, Tsung-Cheng Kuo¹

Affiliations

¹ Department of Obstetrics and Gynecology, Kuo General Hospital, Tainan, Taiwan; Center for Reproductive Medicine, Kuo General Hospital, Tainan, Taiwan.
² Department of Obstetrics and Gynecology, Kuo General Hospital, Tainan, Taiwan; Center for Reproductive Medicine, Kuo General Hospital, Tainan, Taiwan; Department of Laboratory Medicine, Kuo General Hospital, Tainan, Taiwan. Electronic address: kevinwang0518@yahoo.com.tw.
³ Graduate Institute of Pharmacognosy, Taipei Medical University, Taipei, Taiwan.
⁴ Stemforce Biotechnology Co., Ltd, Chiayi, Taiwan.

PMID: 36720532
DOI: 10.1016/j.tjog.2022.08.014

Abstract

Objective: Research has suggested that tumor-initiating tumor stem cells are derived from normal stem cells and that tumor cells undergo progressive de-differentiation to achieve a stem cell-like state. Tumor stem cells are characterized by high proliferation ability, high plasticity, expression of multi-drug resistance proteins, and the ability to seed new tumors. Octamer-binding transcription factor 4 (Oct-4) and its activation targets are overexpressed in the tumor stem cells of various types of tumors, and this expression is associated with the pathogenesis, development, and poor prognosis of tumors. The primary objective of this study was to test if a stably transfected with Oct-4 gene cell line, RL95-2/Oct-4, has the characteristics of tumor stem cells.

Materials and methods: Human endometrial carcinoma cells (RL95-2) were transfected with a plasmid carrying genes for Oct-4 and green fluorescent protein (GFP). The stably transfected cells, RL95-2/Oct-4, were selected using G418 and observed to express the GFP reporter gene under the control of the Oct-4 promoter. GFP expression levels of RL95-2/Oct-4 cells were measured using flow cytometry. The proliferation potential of cells was determined according to cumulative population doubling and colony-formation efficiency. Gene expression was analyzed using reverse transcription-polymerase chain reaction.

Results: RL95-2/Oct-4 cells not only exhibited increased expression of the three most important stem cell genes, Oct-4, Nanog, and Sox2, but also had increased expression of the endometrial tumor stem cell genes CD133 and ALDH1. Furthermore, enhanced expression of these genes in the RL95-2/Oct-4 cells was associated with higher colony-forming ability and growth rate than in parental RL95-2 cells. We also observed that cisplatin induced less cell death in RL95-2/Oct-4 cells than in RL95-2 cells, indicating that RL95-2/Oct-4 cells were more resistant to chemotherapeutic agents.

Conclusion: The study findings contribute to investigate the effects of Oct-4 on tumor stem cell origins.

Keywords: CD133; Chemoresistance; Endometrial carcinoma cells; Oct-4; Tumor stem cells.

MeSH terms

Cell Line, Tumor
Cell Proliferation
Cisplatin* / pharmacology
Drug Resistance, Neoplasm
Endometrial Neoplasms* / drug therapy
Endometrial Neoplasms* / genetics
Endometrial Neoplasms* / metabolism
Female
Humans
Neoplastic Stem Cells / pathology
Octamer Transcription Factor-3* / genetics
Octamer Transcription Factor-3* / metabolism

Substances

Cisplatin
POU5F1 protein, human
Octamer Transcription Factor-3