H-Index
79
Scimago Lab
powered by Scopus
JCR
Clarivate
Analytics
15%
Acceptance
Rate
call: +1.631.470.9640
Mon-Fri 10 am - 2 pm EST

Logo



eISSN: 1643-3750

Get your full text copy in PDF

Glucose-Related Protein 78 Expression and Its Effects on Cisplatin-Resistance in Cervical Cancer

Chengyan Luo, Wen Fan, Yi Jiang, Shulin Zhou, Wenjun Cheng

(Department of Gynecology, Jiangsu Province Hospital, The first Affiliated Hospital with Nanjing Medical University, Nanjing, Jiangsu, China (mainland))

Med Sci Monit 2018; 24:2197-2209

DOI: 10.12659/MSM.906413


BACKGROUND: GRP78, the 78-kDa glucose-regulated protein, occupies a significant position in endoplasmic reticulum stress. Emerging evidences have shown that GRP78 induces chemoresistance in several tumors; however, the role of GRP78 in cervical cancer (CVC) still needs to be elucidated clearly.
MATERIAL AND METHODS: In the present study, we determined the expression levels of GRP78 in CVC tissues collected from patients through immuocytochemistry, western blot and real-time PCR. To evaluate the exact role of GRP78 in CVC cells in the presence of cisplatin, we generated GRP78 knock-down cervical cancer cells through small interfering RNA. After successful transfection, the apoptosis rate was assessed with flow cytometry. The expression levels of caspase-3, CHOP and Bcl-2 in GRP78 knock-down cells were determined by western blot.
RESULTS: The GRP78 levels in CVC tissues were increased significantly. Three types of CVC cells HeLa, SiHa, and C33A were treated with different concentrations of cisplatin and cultured for 12 hours, 24 hours, and 48 hours respectively. And SiHa cells exhibited the highest resistance to cisplatin at all time. Specifically, after 25 μM cisplatin treatment, more than 80% of C33A cells underwent apoptosis, whereas the apoptotic rate of SiHa cells was only 30–40%. Data suggested that GRP78 silencing increased chemo-sensitivity and improved the effects of cisplatin-induced apoptosis in SiHa cells. Moreover, inhibition of GRP78 could upregulate caspase-3 and CHOP expression and downregulate Bcl-2 expression.
CONCLUSIONS: GRP78 may represent a key bio-marker of CVC and silencing GRP78 may strengthen the resistance against cisplatin. GRP78 may be a potential molecular target for CVC therapies in future.

This paper has been published under Creative Common Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) allowing to download articles and share them with others as long as they credit the authors and the publisher, but without permission to change them in any way or use them commercially.
I agree