Establishment and biological characteristics of oxaliplatin-resistant human colon cancer cell lines.
OBJECTIVE
Chemotherapy is the main treatment for colon cancer, while multidrug-resistance is the main reason for chemotherapy failure and tumor relapse. This study was to establish two oxaliplatin-resistant colon cancer cell lines and evaluate their biological characteristics.


METHODS
Oxaliplatin-resistant colon cancer cell lines SW620/L-OHP and lovo/L-OHP were established in vitro by continuous exposure to oxaliplatin (L-OHP) of low and gradually increased concentration. Growth curve, cross-resistance and resistance index of the oxaliplatin-resistant cell lines to various anti-cancer agents were determined by CCK8 assay. The expressions of P-glycoprotein (P-gp), multidrug-resistance protein 1 (MRP1) and MRP2 were detected by Western blot. Cell cycle distribution as well as the expression of CD133 and CD44 were measured by flow cytometry.


RESULTS
It took 10 months to establish the SW620/L-OHP and LoVo/L-OHP cell lines with stable resistance to oxaliplatin. Cross-resistance to 5-fluorouracil, etoposide, cisplatin, vincristine and epirubicin but not to paclitaxel was observed. Longer doubling time, higher proportion of cells in G(0)/G(1) phase and lower proportion in G(2)/M phase were observed in the two oxaliplatin-resistant cell lines compared with their parental cell lines. The expression of MRP2 in the oxaliplatin-resistant cells was up-regulated, while those of P-gp and MRP1 had no significant change. CD133 was overexpressed while CD44 level remained unchanged in SW620/L-OHP and LoVo/L-OHP cells.


CONCLUSIONS
SW620/L-OHP and LoVo/L-OHP cell lines show a typical and stably resistant phenotype and may be used as research models.
Liu
Zhen
Z
Department of Medical Oncology ,West China Hospital, Sichuan University, Chengdu, Sichuan 610041, PR China.
Qiu
Meng
M
Tang
Qiu-Lin
QL
Liu
Ming
M
Lang
Nan
N
Bi
Feng
F
D000071916:AC133 Antigen; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D015703:Antigens, CD / Q000378:metabolism; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D002453:Cell Cycle; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology*; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D015251:Epirubicin / Q000494:pharmacology; D005047:Etoposide / Q000494:pharmacology; D005472:Fluorouracil / Q000494:pharmacology; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000378:metabolism; D009944:Organoplatinum Compounds / Q000494:pharmacology*; D000077150:Oxaliplatin; D010455:Peptides / Q000378:metabolism; D014750:Vincristine / Q000494:pharmacology
D000071916:AC133 Antigen; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000903:Antibiotics, Antineoplastic; D015703:Antigens, CD; D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D002945:Cisplatin; D015251:Epirubicin; D005047:Etoposide; D005472:Fluorouracil; D006023:Glycoproteins; D018960:Hyaluronan Receptors; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D010455:Peptides; D014750:Vincristine; C000715087:ABCC2 protein, human; C497483:CD44 protein, human; C000606023:PROM1 protein, human; C421109:multidrug resistance-associated protein 1