Login Register Cart 0
Generic placeholder image

Anti-Cancer Agents in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Knockdown of PROM2 Enhances Paclitaxel Sensitivity in Endometrial Cancer Cells by Regulating the AKT/FOXO1 Pathway

Author(s): Jun Jiang, Chen Zhang, Jianfen Wang, Yingping Zhu, Xinyan Wang and Peiyu Mao*

Volume 23, Issue 19, 2023

Published on: 12 September, 2023

Page: [2127 - 2134] Pages: 8

DOI: 10.2174/1871520623666230905104555

Price: $65

Abstract

Background: Endometrial cancer is a very common and highly lethal reproductive malignant tumour in women. Paclitaxel (PTX) is a usual drug utilized in chemotherapy for endometrial cancer. It has been uncovered that PROM2 participates in the progression of various cancers through playing a promoter. However, the regulatory function of PROM2 in PTX treatment for endometrial cancer remains unclear.

Methods: The cell viability (IC50) was examined through CCK8 assay. The mRNA and protein expressions of genes were measured through RT-qPCR and western blot. The proliferation was evaluated through colony formation and EdU assays. The cell apoptosis was assessed through flow cytometry.

Results: In this work, through bioinformatic analysis on online websites, it is found that the up-regulated expression of PROM2 existed in endometrial cancer. In addition, the survival probability of UCEC patients with high PROM2 expression was worse. This study adopted PTX treatment for obtaining the PTX-resistant cells (HEC-1A/PTX and KLE/PTX). Furthermore, suppression of PROM2 enhanced PTX sensitivity through decreasing IC50 and proliferation in endometrial cancer. Additionally, knockdown of PROM2 facilitated cell apoptosis in HEC-1A/PTX and KLE/PTX cells. Next, we found that silencing of PROM2 retards the AKT/FOXO1 pathway. At last, rescue assays reversed the strengthened PTX sensitivity mediated by PROM2 inhibition after SC79 treatment (AKT activator).

Conclusion: Knockdown of PROM2 enhanced PTX sensitivity in endometrial cancer through modulating the AKT/FOXO1 pathway. This study hinted that PROM2 may be a useful therapeutic target for PTX treatment in endometrial cancer.

« Previous Next »
[1]
Amant, F.; Moerman, P.; Neven, P.; Timmerman, D.; Van Limbergen, E.; Vergote, I. Endometrial cancer. Lancet, 2005, 366(9484), 491-505.
[http://dx.doi.org/10.1016/S0140-6736(05)67063-8] [PMID: 16084259]
[2]
Bakir, M.S.; Birge, O.; Karadag, C.; Dogan, S.; Tuncer, H.A.; Simsek, T. Clinicopathological risk factors and survival analysis of ovarian cancer with synchronous endometrial cancer diagnosed after surgery. Eur. J. Gynaecol. Oncol., 2021, 42(3), 499-505.
[http://dx.doi.org/10.31083/j.ejgo.2021.03.2336]
[3]
Wan-Nor-Asyikeen, W.A.; Siti-Azrin, A.H.; Jalil, N.A.; Othman, N.H.; Zain, A.A. Endometrial cancer in hospital universiti sains malaysia. Asian Pac. J. Cancer Prev., 2016, 17(6), 2867-2870.
[PMID: 27356704]
[4]
Braun, M.M.; Overbeek-Wager, E.A.; Grumbo, R.J. Diagnosis and management of endometrial cancer. Am. Fam. Physician, 2016, 93(6), 468-474.
[PMID: 26977831]
[5]
Her, E-J.; Kwon, H.; Chae, B.; Kim, Y-J.; Lee, Y-S. High D-dimer is a predictor for short-term mortality in patients with active cancer and acute pulmonary embolism. Signa Vitae, 2021, 17(5), 58-63.
[6]
Kim, M.K.; Choi, M.C.; Lim, M.C.; Kim, J-W. Practice patterns for Lynch syndrome-associated endometrial cancer management in Korea. Eur. J. Gynaecol. Oncol., 2021, 42(4), 737-741.
[http://dx.doi.org/10.31083/j.ejgo4204111]
[7]
Pérez-Herrero, E.; Fernández-Medarde, A. Advanced targeted therapies in cancer: Drug nanocarriers, the future of chemotherapy. Eur. J. Pharm. Biopharm., 2015, 93, 52-79.
[http://dx.doi.org/10.1016/j.ejpb.2015.03.018] [PMID: 25813885]
[8]
Gómez-Raposo, C.; Merino Salvador, M.; Aguayo Zamora, C.; Casado Saenz, E. Adjuvant chemotherapy in endometrial cancer. Cancer Chemother. Pharmacol., 2020, 85(3), 477-486.
[http://dx.doi.org/10.1007/s00280-019-04027-6] [PMID: 31950214]
[9]
Bestvina, C.M.; Fleming, G.F. Chemotherapy for endometrial cancer in adjuvant and advanced disease settings. Oncologist, 2016, 21(10), 1250-1259.
[http://dx.doi.org/10.1634/theoncologist.2016-0062] [PMID: 27412393]
[10]
Saha, S.K.; Islam, S.M.R.; Kwak, K.S.; Rahman, M.S.; Cho, S.G. PROM1 and PROM2 expression differentially modulates clinical prognosis of cancer: A multiomics analysis. Cancer Gene Ther., 2020, 27(3-4), 147-167.
[http://dx.doi.org/10.1038/s41417-019-0109-7] [PMID: 31164716]
[11]
Lee, J.; Shin, J.E.; Lee, B.; Kim, H.; Jeon, Y.; Ahn, S.H.; Chi, S.W.; Cho, Y. The stem cell marker Prom1 promotes axon regeneration by down-regulating cholesterol synthesis via Smad signaling. Proc. Natl. Acad. Sci. USA, 2020, 117(27), 15955-15966.
[http://dx.doi.org/10.1073/pnas.1920829117] [PMID: 32554499]
[12]
Florek, M.; Bauer, N.; Janich, P.; Wilsch-Braeuninger, M.; Fargeas, C.A.; Marzesco, A.M.; Ehninger, G.; Thiele, C.; Huttner, W.B.; Corbeil, D. Prominin-2 is a cholesterol-binding protein associated with apical and basolateral plasmalemmal protrusions in polarized epithelial cells and released into urine. Cell Tissue Res., 2007, 328(1), 31-47.
[http://dx.doi.org/10.1007/s00441-006-0324-z] [PMID: 17109118]
[13]
Barzegar Behrooz, A.; Syahir, A.; Ahmad, S. CD133: Beyond a cancer stem cell biomarker. J. Drug Target., 2019, 27(3), 257-269.
[http://dx.doi.org/10.1080/1061186X.2018.1479756] [PMID: 29911902]
[14]
Li, W.; Zhu, Y.; Zhang, K.; Yu, X.; Lin, H.; Wu, W.; Peng, Y.; Sun, J. PROM2 promotes gemcitabine chemoresistance via activating the Akt signaling pathway in pancreatic cancer. Exp. Mol. Med., 2020, 52(3), 409-422.
[http://dx.doi.org/10.1038/s12276-020-0390-4] [PMID: 32123287]
[15]
Luo, W.; Wang, J.; Xu, W.; Ma, C.; Wan, F.; Huang, Y.; Yao, M.; Zhang, H.; Qu, Y.; Ye, D.; Zhu, Y. LncRNA RP11-89 facilitates tumorigenesis and ferroptosis resistance through PROM2-activated iron export by sponging miR-129-5p in bladder cancer. Cell Death Dis., 2021, 12(11), 1043.
[http://dx.doi.org/10.1038/s41419-021-04296-1] [PMID: 34728613]
[16]
Bao, L.; Zhang, Y.; Wang, J.; Wang, H.; Dong, N.; Su, X.; Xu, M.; Wang, X. Variations of chromosome 2 gene expressions among patients with lung cancer or non-cancer. Cell Biol. Toxicol., 2016, 32(5), 419-435.
[http://dx.doi.org/10.1007/s10565-016-9343-z] [PMID: 27301951]
[17]
Yen, T.T.; Wang, T.L.; Fader, A.N.; Shih, I.M.; Gaillard, S. Molecular classification and emerging targeted therapy in endometrial cancer. Int. J. Gynecol. Pathol., 2020, 39(1), 26-35.
[http://dx.doi.org/10.1097/PGP.0000000000000585]
[18]
Zarrin, H.; Ko, E.; Haggerty, A.; Latif, N.; Kim, S.; Cory, L. Comparative survival outcomes among high risk endometrial cancers. Eur. J. Gynaecol. Oncol., 2021, 42(2), 386-387.
[19]
Alqahtani, F.Y.; Aleanizy, F.S.; El Tahir, E.; Alkahtani, H.M.; AlQuadeib, B.T. Paclitaxel. Profiles Drug Subst. Excip. Relat. Methodol., 2019, 44, 205-238.
[http://dx.doi.org/10.1016/bs.podrm.2018.11.001] [PMID: 31029218]
[20]
Chaudhry, P.; Asselin, E. Resistance to chemotherapy and hormone therapy in endometrial cancer. Endocr. Relat. Cancer, 2009, 16(2), 363-380.
[http://dx.doi.org/10.1677/ERC-08-0266] [PMID: 19190080]
[21]
Fernandes, C.; Prabhu, P.; Juvale, K.; Suares, D.; Yc, M. Cancer cell fusion: A potential target to tackle drug-resistant and metastatic cancer cells. Drug Discov. Today, 2019, 24(9), 1836-1844.
[http://dx.doi.org/10.1016/j.drudis.2019.05.024] [PMID: 31163272]
[22]
Bruce, S.F.; Cho, K.; Noia, H.; Lomonosova, E.; Stock, E.C.; Oplt, A.; Blachut, B.; Mullen, M.M.; Kuroki, L.M.; Hagemann, A.R.; McCourt, C.K.; Thaker, P.H.; Khabele, D.; Powell, M.A.; Mutch, D.G.; Shriver, L.P.; Patti, G.J.; Fuh, K.C. GAS6-AXL inhibition by AVB-500 overcomes resistance to paclitaxel in endometrial cancer by decreasing tumor cell glycolysis. Mol. Cancer Ther., 2022, 21(8), 1348-1359.
[http://dx.doi.org/10.1158/1535-7163.MCT-21-0704] [PMID: 35588308]
[23]
Yanokura, M.; Banno, K.; Aoki, D. MicroRNA 34b expression enhances chemosensitivity of endometrial cancer cells to paclitaxel. Int. J. Oncol., 2020, 57(5), 1145-1156.
[http://dx.doi.org/10.3892/ijo.2020.5127] [PMID: 33300049]
[24]
Yi, H.; Han, Y.; Li, S. Oncogenic circular RNA circ_0007534 contributes to paclitaxel resistance in endometrial cancer by sponging miR-625 and promoting ZEB2 expression. Front. Oncol., 2022, 12, 985470.
[http://dx.doi.org/10.3389/fonc.2022.985470] [PMID: 35992812]
[25]
Abraham, E. Akt/protein kinase B. Crit. Care Med., 2005, 33(12)(Suppl.), S420-S422.
[http://dx.doi.org/10.1097/01.CCM.0000191715.31970.D8] [PMID: 16340410]
[26]
Qiu, J.; Zhang, Y.; Xie, M. Chrysotoxine attenuates sevoflurane-induced neurotoxicity in vitro via regulating PI3K/AKT/GSK pathway. Signa Vitae, 2021, 17(4), 185-191.
[27]
Liao, J.; Chen, H.; Qi, M.; Wang, J.; Wang, M. MLLT11-TRIL complex promotes the progression of endometrial cancer through PI3K/AKT/mTOR signaling pathway. Cancer Biol. Ther., 2022, 23(1), 211-224.
[http://dx.doi.org/10.1080/15384047.2022.2046450] [PMID: 35253622]
[28]
Link, W. Introduction to FOXO Biology. Methods Mol. Biol., 2019, 1890, 1-9.
[http://dx.doi.org/10.1007/978-1-4939-8900-3_1] [PMID: 30414140]
[29]
Xing, Y.; Li, A.; Yang, Y.; Li, X.; Zhang, L.; Guo, H. The regulation of FOXO1 and its role in disease progression. Life Sci., 2018, 193, 124-131.
[http://dx.doi.org/10.1016/j.lfs.2017.11.030] [PMID: 29158051]
[30]
Ma, L.; Sun, Y.; Li, D.; Li, H.; Jin, X.; Ren, D. Overexpressed ITGA2 contributes to paclitaxel resistance by ovarian cancer cells through the activation of the AKT/FoxO1 pathway. Aging (Albany NY), 2020, 12(6), 5336-5351.
[http://dx.doi.org/10.18632/aging.102954] [PMID: 32202508]
[31]
Lu, Z.; Xu, Y.; Yao, Y.; Jiang, S. miR-205-5p contributes to paclitaxel resistance and progression of endometrial cancer by downregulating FOXO1. Oncol. Res., 2019. Epub ahead of print
[http://dx.doi.org/10.3727/096504018X15452187888839] [PMID: 30982496]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy