[Correlation of chemosensitivity tested using histoculture drug response assay to expression of multidrug resistance genes and proteins in colorectal cancer tissues].
OBJECTIVE
The therapeutic effects of chemotherapy for malignant neoplasms are still unsatisfactory. This study was to evaluate the chemosensitivity of colorectal cancer tissues to therapeutic agents using histoculture drug response assay (HDRA), and explore the correlation of chemosensitivity to the expression levels of multidrug resistance (MDR) genes and proteins.


METHODS
Twenty-two specimens of colorectal cancer were collected. The inhibition rates of single agents, including epirubicin, cisplatin (DDP), oxaliplatin, 5-FU, taxetere, irinotecan, and combinations of these agents, including 5-FU+epirubicin+DDP, 5-FU+irinotecan, 5-FU+oxaliplatin, 5-FU+taxetere+ DDP on colorectal cancer tissues were evaluated by HDRA. The agent whose inhibition rate was greater than 30% was considered sensitive, and the sensitivity was calculated. mRNA and protein levels of MDR genes and proteins in colorectal cancer tissues were measured by RT-PCR and immunohistochemistry.


RESULTS
Among the single agents, the inhibition rate of oxaliplatin (17.5%) and sensitivity of cancer tissues to 5-FU (36.4%) were the highest. In the combination groups of agents, the inhibition rate of 5-FU+ oxaliplatin (54.1%), and sensitivity of cancer tissues to 5-FU+epirubicin+DDP (71.4%) and to 5-FU+taxetere+DDP (71.4%) were the highest. The inhibition rates of and sensitivity of cancer tissues to combined agents were higher than those of single agents (P<0.05). Expressions of MDR1, multidrug resistance protein-1 (MRP1), ABC-binding cassette transporter superfamily-G-2 (ABCG2) mRNA were detected in 88.9%, 55.6% and 55.6% of specimens respectively; while those of MDR1, MRP1 and ABCG2 proteins were detected in 55.6%, 33.3%, and 50.0% of specimens respectively. Expressions of mRNA and proteins had no correlation in MDR1, MRP1 and ABCG2 (P>0.05). High expression of ABCG2 protein was correlated to the resistance of colorectal cancer cells to epirubicin (P<0.05).


CONCLUSIONS
Expressions of MDR proteins are correlated to chemosensitivity of colorectal cancer to some extents. By combining HDRA with measurement of MDR genes and proteins, chemosensitivity of individual tumors may be predicted to guide selection of effective chemotherapeutic agents.
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
Qiu
Hai-Bo
HB
Zhang
Li-Yi
LY
D018435:ATP Binding Cassette Transporter, Subfamily B; 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*; D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D002945:Cisplatin / Q000008:administration & dosage; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor / Q000379:methods*; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000494:pharmacology; D019450:Genes, MDR; D006801:Humans; D008297:Male; D008875:Middle Aged; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000494:pharmacology; D000077150:Oxaliplatin; D012333:RNA, Messenger / Q000378:metabolism; D012004:Rectal Neoplasms / Q000378:metabolism / Q000473:pathology
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D002945:Cisplatin; D015251:Epirubicin; D005472:Fluorouracil; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009363:Neoplasm Proteins; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D012333:RNA, Messenger; C513055:ABCB1 protein, human; C116614:ABCG2 protein, human; C421109:multidrug resistance-associated protein 1