BACKGROUND AND OBJECTIVEThe expression levels of glucose-regulated protein 78 (GRP78) were elevated and correlated with resistance to chemotherapy drug VP-16 in lung cancer cells. However, little is known about the relationship between its expression and resistance to cisplatin in lung cancer cells. The aim of this study was to investigate the expression of GRP78 under the induction of A23187 and its significance in the resistance to anti-tumor drugs cisplatin in a human lung cancer SPCA-1 cell line.

METHODSRT-PCR and Western blot were used to analyze the expression of GRP78 at mRNA and protein levels in SPCA-1 cell line induced byA23187 at different concentrations (0, 1, 2, 4, 6 microM). MTT was used to determine the effect of cisplation on cell survival.

RESULTSThe expressions of GRP78 at both mRNA and protein levels were increased obviously in SPCA-1 cell line induced by A23187, with a manner of dose-dependent of A23187 to a great degree; MTT assay showed that the cell survival rate of the A23187-induced group decreased significantly compare to the control group, also with a concentration-dependent manner of A23187.

CONCLUSIONThe expression of GRP78 at both mRNA and protein levels were increased obviously in SPCA-1 cell line induced by A23187. The enhancement of GRP78 showed a negative correlation with the cell survival rate treated by cisplatin. All these indicated that overexpression of GRP78 can enhance the sensitivity to cisplatin and there is correlation between the expression of GRP78 and resistance to cisplatin of human lung cancer SPCA-1 cell line.

Antineoplastic Agents ; pharmacology ; Blotting, Western ; Calcimycin ; pharmacology ; Cell Line, Tumor ; Cell Survival ; drug effects ; Cisplatin ; pharmacology ; Drug Resistance, Neoplasm ; genetics ; physiology ; Heat-Shock Proteins ; genetics ; metabolism ; Humans ; Reverse Transcriptase Polymerase Chain Reaction

Nasopharyngeal carcinoma (NPC) is a malignant tumor that mainly occurs in East and Southeast Asia. Although patients benefit from the main NPC treatments (e.g., radiotherapy and concurrent chemotherapy), persistent and recurrent diseases still occur in some NPC patients. Therefore, investigating the pathogenesis of NPC is of great clinical significance. In the present study, replication factor c subunit 4 (RFC4) is a key potential target involved in NPC progression via bioinformatics analysis. Furthermore, the expression and mechanism of RFC4 in NPC were investigated in vitro and in vivo. Our results revealed that RFC4 was more elevated in NPC tumor tissues than in normal tissues. RFC4 knockdown induced G2/M cell cycle arrest and inhibited NPC cell proliferation in vitro and in vivo. Interestingly, HOXA10 was confirmed as a downstream target of RFC4, and the overexpression of HOXA10 attenuated the silencing of RFC4-induced cell proliferation, colony formation inhibition, and cell cycle arrest. For the first time, this study reveals that RFC4 is required for NPC cell proliferation and may play a pivotal role in NPC tumorigenesis.
Humans ; Nasopharyngeal Carcinoma/pathology* ; Carcinoma/pathology* ; Replication Protein C/metabolism* ; Nasopharyngeal Neoplasms/pathology* ; Cell Line, Tumor ; Cell Proliferation ; Gene Expression Regulation, Neoplastic ; Cell Movement