[Correlation of chemosensitivity measured by histoculture drug response assay to expression of multidrug resistance genes and proteins in gastric cancer].
OBJECTIVE
The therapeutic effects of chemotherapy on gastric cancer are still unsatisfactory. Predicting chemosensitivity of tumors as therapeutic guidance could help to improve the efficacy of chemotherapy. This study was to evaluate the chemosensitivity of gastric cancer to single or combined therapeutic agents by histoculture drug response assay, to evaluate the expression levels of multidrug resistance (MDR) genes and proteins and analyze their correlations to the chemosensitivity of gastric cancer.


METHODS
The inhibitory effects of single agents, including epirubicin, cisplatin (DDP), oxaliplatin, 5-fluorouracil (5-FU), taxetere, irinotecan, and combined regimens, including 5-FU, epirubicin plus DDP, 5-FU plus irinotecan, 5-FU plus oxaliplatin, and 5-FU, taxetere plus DDP, on 22 specimens of gastric cancer were evaluated by histoculture drug response assay. The mRNA and protein expression of MDR1, MRP1 and ABCG2 in gastric cancer were detected by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry.


RESULTS
The inhibition rate of gastric cancer by 5-FU (29.8%) and sensitivity of gastric cancer to 5-FU (50.0%) were the highest among single agents; the inhibition rate of gastric cancer by 5-FU, taxetere plus DDP (59.8%) and sensitivity to 5-FU, epirubicin plus DDP (77.3%) were the highest among combined regimens; combined regimens achieved higher inhibition rate and sensitivity as compared with single agents (P<0.05). The positive rates of MDR1, MRP1, and ABCG2 mRNA were 90.9%, 54.5%, and 77.3%; the positive rates of MDR1, MRP1, and ABCG2 proteins were 36.4%, 54.5%, and 36.4%. High expression of MDR proteins in gastric cancer was related with the resistance to epirubicin (P<0.05).


CONCLUSIONS
High expression of MDR1, MRP1, ABCG2 proteins in gastric cancer is related with the resistance to epirubicin, which indicates that these MDR genes may play a role in conferring the drug resistance to epirubicin.
Yuan
Shu-Qiang
SQ
State Key Laboratory of Oncology in South China, Guangzhou, Guangdong, 510060, PR China.
Zhou
Zhi-Wei
ZW
Liang
Yong-Ju
YJ
Fu
Li-Wu
LW
Chen
Gong
G
Keshari
Rajiv Prasad
RP
Zhang
Li-Yi
LY
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism*; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005472:Fluorouracil / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D019450:Genes, MDR; D006801:Humans; D007150:Immunohistochemistry; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D013274:Stomach Neoplasms / Q000473:pathology*; D014407:Tumor Cells, Cultured
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D000964:Antimetabolites, Antineoplastic; D005472:Fluorouracil; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; C116614:ABCG2 protein, human; C421109:multidrug resistance-associated protein 1