Logo Medical Science Monitor

Call: +1.631.470.9640
Mon - Fri 10:00 am - 02:00 pm EST

Contact Us

Logo Medical Science Monitor Logo Medical Science Monitor Logo Medical Science Monitor

31 July 2017 : Laboratory Research  

Regenerating Family Member 4 (Reg4) Enhances 5-Fluorouracil Resistance of Gastric Cancer Through Activating MAPK/Erk/Bim Signaling Pathway

Jiaoyue Jin1BE, Hang Lv2CG, Junzhou Wu1CD, Dan Li1BC, Kaiyan Chen1BF, Fanrong Zhang1BF, Jing Han3B, Jianguo Feng1CD, Nan Zhang1F, Herbert Yu4F, Dan Su1AG, Lisha Ying1A*

DOI: 10.12659/MSM.903134

Med Sci Monit 2017; 23:3715-3721

Abstract

BACKGROUND: Reg4, a member of the Reg multigene family, is highly upregulated in many gastrointestinal cancers including gastric cancer (GC). The enhanced expression of Reg4 is associated with the resistance of GC to 5-fluorouracil (5-FU), while the underlying mechanism is not clear. The aim of the present study was to explore the resistant mechanism underlying 5-FU resistance.

MATERIAL AND METHODS: Reg4 expression was assessed by Western blot analysis for SGC-7901, BGC-823, AGS, MKN28, and MKN45. Synthetic short single strand RNA oligonucleotides and Flag-Reg4 plasmid were used to investigate the biological function of Reg4 in vitro. The cell viability assay was performed by MTT. Flow cytometry was carried out to measure the apoptosis caused by 5-FU. Reverse-transcriptase quantitative polymerase chain reaction (RT-qPCR) was used to examine the expression of 5-FU metabolism related enzymes. The effect of Reg4 on intracellular signaling was evaluated by Western blot.

RESULTS: Western blot analysis of 5 GC cells showed that Reg4 was low or null in SGC-7901 and BGC-823, while high in AGS, MKN28, and MKN45. Over-expression of flag-Reg4 in SGC-7901 led to an increase in cell viability and lower apoptosis with 5-FU treatment. In contrast, siRNA knockdown of Reg4 enhanced 5-FU induced apoptosis. However, over-expression or knockdown of Reg4 had no significant influence on the expression of 5-FU metabolic enzymes. Further investigation revealed that Reg4 could activate Erk1/2-Bim-caspase3 cascade.

CONCLUSIONS: Reg4 inhibited apoptosis through regulating MAPK/Erk/Bim signaling pathway and thereby enhanced the resistance of GC to 5-FU.

Keywords: Fluorouracil, Stomach Neoplasms

0 Comments

Editorial

01 October 2022 : Editorial  

Editorial: Rebound COVID-19 and Cessation of Antiviral Treatment for SARS-CoV-2 with Paxlovid and Molnupiravir

Dinah V. Parums
Science Editor, Medical Science Monitor, International Scientific Information, Inc., Melville, NY, USA

DOI: 10.12659/MSM.938532

Med Sci Monit 2022; 28:e938532

SARS-CoV-2/COVID-19

16 September 2022 : Review article  

Effects of Physiotherapy on Rehabilitation and Quality of Life in Patients Hospitalized for COVID-19: A Rev...

Med Sci Monit In Press; DOI: 10.12659/MSM.938141  

03 October 2022 : Clinical Research  

Effect of Vitamin D Concentration on Course of COVID-19

Med Sci Monit 2022; 28:e937741

In Press

30 Sep 2022 : Clinical Research  

Correlation Between Trough Level of Abiraterone and Prostate-Specific Antigen (PSA) Response in Metastatic ...

Med Sci Monit In Press; DOI: 10.12659/MSM.938091  

30 Sep 2022 : Review article  

A Review of the Biological Mechanisms of Dexmedetomidine for Postoperative Neurocognitive Disorders

Med Sci Monit In Press; DOI: 10.12659/MSM.937862  

29 Sep 2022 : Animal Research  

Effect of Antilogous Platelet-Rich Plasma on the Revascularization of Rabbit Prefabricated Flap

Med Sci Monit In Press; DOI: 10.12659/MSM.937718  

26 Sep 2022 : Clinical Research  

Distribution and Determinants of Plasma Homocysteine Levels in a Preconception Population: A Retrospective ...

Med Sci Monit In Press; DOI: 10.12659/MSM.937987  

Most Viewed Current Articles

30 Dec 2021 : Clinical Research  

Retrospective Study of Outcomes and Hospitalization Rates of Patients in Italy with a Confirmed Diagnosis o...

DOI :10.12659/MSM.935379

Med Sci Monit 2021; 27:e935379

13 Nov 2021 : Clinical Research  

Acceptance of COVID-19 Vaccination and Its Associated Factors Among Cancer Patients Attending the Oncology ...

DOI :10.12659/MSM.932788

Med Sci Monit 2021; 27:e932788

08 Mar 2022 : Review article  

A Review of the Potential Roles of Antioxidant and Anti-Inflammatory Pharmacological Approaches for the Man...

DOI :10.12659/MSM.936292

Med Sci Monit 2022; 28:e936292

01 Nov 2020 : Review article  

Long-Term Respiratory and Neurological Sequelae of COVID-19

DOI :10.12659/MSM.928996

Med Sci Monit 2020; 26:e928996

Your Privacy

We use cookies to ensure the functionality of our website, to personalize content and advertising, to provide social media features, and to analyze our traffic. If you allow us to do so, we also inform our social media, advertising and analysis partners about your use of our website, You can decise for yourself which categories you you want to deny or allow. Please note that based on your settings not all functionalities of the site are available. View our privacy policy.

Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750