Increased expression of GRP94 protein is associated with decreased sensitivity to adriamycin in ovarian carcinoma cell lines.
OBJECTIVE
This study examined the involvement of glucose regulated protein 94 (GRP94) in chemotherapy-resistance in human ovarian cancer cells.


METHODS
Three human ovarian cancer cells were examined for basal levels of GRP94 mRNA by RT-PCR and protein by Western blotting. Sensitivities to adriamycin of these cell lines were determined by means of MTT assay. The suppression of GRP94 expression was performed using specific siRNA in HO-8910PM cells, and cell apoptosis was assessed by flow cytometry. One-way ANOVA and the Student-Newman-Keuls test were used to determine which were significantly different.


RESULTS
HO-8910PM cells, with the highest basal levels of GRP94, exhibited the lowest sensitivity to adriamycin. In HO-8910PM cells, the sensitivity to adriamycin was increased when the GRP94 gene was disturbed by specific siRNA transfection.


CONCLUSIONS
High GRP94 expression might be one of the molecular mechanisms causing resistance to adriamycin, and therefore GRP94 siRNA maybe useful in tumor-specific gene therapy in ovarian cancer.
Zhang
L Y
LY
Department of Gynecology and Obstetrics, Second Affiliated Hospital of Harbin Medical University, Harbin, China.
Zhang
X C
XC
Wang
L D
LD
Zhang
Z F
ZF
Li
P L
PL
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics*; D034741:RNA, Small Interfering / Q000502:physiology
D000903:Antibiotics, Antineoplastic; D008562:Membrane Glycoproteins; D034741:RNA, Small Interfering; C053387:endoplasmin; D004317:Doxorubicin