Ribosomal proteins S13 and L23 promote multidrug resistance in gastric cancer cells by suppressing drug-induced apoptosis.
Ribosomal proteins (RP) S13 and RPL23 were previously identified as two upregulated genes in a multidrug-resistant gastric cancer cell line SGC7901/VCR compared to its parental cell SGC7901 by differential display PCR. The aim of this study was to explore the roles of RPS13 and RPL23 in multidrug resistance (MDR) in gastric cancer cells. RPS13 and RPL23 were genetically overexpressed in SGC7901 cells, respectively. Either RPS13 or RPL23 enhanced resistance of SGC7901 cells to vincristine, adriamycin, and 5-fludrouracil. RPL23 also enhanced resistance of SGC7901 cells to cisplatin. Overexpression of either RPS13 or RPL23 did not alter the population doubling time, [3H]leucine incorporation, and intracellular adriamycin accumulation of SGC7901 cells. However, either RPS13 or RPL23 could protect SGC7901 cells from undergoing vincristine-induced apoptosis. Western blot analysis revealed that both RPS13 and RPL23 significantly increased the expression level of Bcl-2 and Bcl-2/Bax ratio in SGC7901 cells. In addition, overexpression of RPL23 enhanced glutathione S-transferase (GST) activity and intracellular glutathione content in SGC7901 cells. Together, this work demonstrates that either RPS13 or RPL23 can promote MDR in gastric cancer cells by suppressing drug-induced apoptosis, and that RPL23 may also promote MDR in gastric cancer cells through regulation of glutathione S-transferase-mediated drug-detoxifying system.
Shi
Yongquan
Y
Institute of Digestive Diseases, Xijing Hospital, The Fourth Military Medical University, Xi'an 710032, Shaanxi Province, China.
Zhai
Huihong
H
Wang
Xin
X
Han
Zheyi
Z
Liu
Changjiang
C
Lan
Mei
M
Du
Jingping
J
Guo
Changcun
C
Zhang
Yumei
Y
Wu
Kaichun
K
Fan
Daiming
D
D017209:Apoptosis / Q000187:drug effects; D002455:Cell Division; D045744:Cell Line, Tumor; D018432:Drug Resistance, Multiple; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D009363:Neoplasm Proteins / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000032:analysis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D012269:Ribosomal Proteins / Q000235:genetics / Q000502:physiology*; D013274:Stomach Neoplasms / Q000473:pathology*; D014162:Transfection; D014750:Vincristine / Q000494:pharmacology; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; C047013:RPS13 protein, human; D012269:Ribosomal Proteins; D051028:bcl-2-Associated X Protein; C032493:ribosomal protein L17; D014750:Vincristine; D005982:Glutathione Transferase