Regulation of multidrug resistance by ribosomal protein l6 in gastric cancer cells.
Ribosomal proteins (RP) L6 was previously identified as an up-regulated gene in multidrug-resistant gastric cancer cells SGC7901/ADR comparing to its parental cells SGC7901 by subtractive hybridization. The aim of this study was to explore the roles of RPL6 in multidrug resistance (MDR) in gastric cancer cells. Northern and Western blot analysis confirmed that RPL6 was overexpressed in SGC7901/ADR cells. By gene transfection, RPL6 was genetically upregulated in SGC7901 or down-regulated in SGC7901/ ADR cells. Upregulation of RPL6 was associated with enhanced resistance to multiple anticancer drugs (adriamycin, vincristine, etoposide, 5-fluorouracil and cisplatin) and to adriamycin-induced apoptosis. Downregulation of RPL6 reversed MDR and sensitized cells to adriamycin-induced apoptosis. Alteration of RPL6 showed no obvious influence on intracellular adriamycin accumulation, glutathione content and expression of glutathione S-transferase. RPL6 could upregulate Bcl-2 and downregulate Bax in cells. Together, this work demonstrates that RPL6 could regulate MDR in gastric cancer cells by suppressing drug-induced apoptosis.
Du
Jingping
J
Institute of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Shaanxi Province, People's Republic of China.
Shi
Yongquan
Y
Pan
Yanglin
Y
Jin
Xiaohang
X
Liu
Changjiang
C
Liu
Na
N
Han
Quanli
Q
Lu
Yuanyuan
Y
Qiao
Taidong
T
Fan
Daiming
D
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D015152:Blotting, Northern; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology; D018432:Drug Resistance, Multiple; D005047:Etoposide / Q000494:pharmacology; D005472:Fluorouracil / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D005978:Glutathione / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012269:Ribosomal Proteins / Q000235:genetics / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D014162:Transfection; D014750:Vincristine / Q000494:pharmacology; D051028:bcl-2-Associated X Protein
D000903:Antibiotics, Antineoplastic; D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; C494826:BAX protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D012269:Ribosomal Proteins; D051028:bcl-2-Associated X Protein; C031249:ribosomal protein L6; D014750:Vincristine; D005047:Etoposide; D004317:Doxorubicin; D005982:Glutathione Transferase; D005978:Glutathione; D002945:Cisplatin; D005472:Fluorouracil