Establishment and biological characteristics of oxaliplatin-resistant human colon cancer cell lines

Chin J Cancer. 2010 Jul;29(7):661-7. doi: 10.5732/cjc.009.10666.

Abstract

Background and 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AC133 Antigen
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
  • Antibiotics, Antineoplastic / pharmacology
  • Antigens, CD / metabolism
  • Antimetabolites, Antineoplastic / pharmacology
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents, Phytogenic / pharmacology
  • Cell Cycle
  • Cell Line, Tumor*
  • Cisplatin / pharmacology
  • Colonic Neoplasms / metabolism
  • Colonic Neoplasms / pathology*
  • Drug Resistance, Multiple*
  • Drug Resistance, Neoplasm*
  • Epirubicin / pharmacology
  • Etoposide / pharmacology
  • Fluorouracil / pharmacology
  • Glycoproteins / metabolism
  • Humans
  • Hyaluronan Receptors / metabolism
  • Multidrug Resistance-Associated Protein 2
  • Multidrug Resistance-Associated Proteins / metabolism
  • Organoplatinum Compounds / pharmacology*
  • Oxaliplatin
  • Peptides / metabolism
  • Vincristine / pharmacology

Substances

  • ABCC2 protein, human
  • AC133 Antigen
  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Antibiotics, Antineoplastic
  • Antigens, CD
  • Antimetabolites, Antineoplastic
  • Antineoplastic Agents
  • Antineoplastic Agents, Phytogenic
  • CD44 protein, human
  • Glycoproteins
  • Hyaluronan Receptors
  • Multidrug Resistance-Associated Protein 2
  • Multidrug Resistance-Associated Proteins
  • Organoplatinum Compounds
  • PROM1 protein, human
  • Peptides
  • Oxaliplatin
  • Epirubicin
  • Vincristine
  • Etoposide
  • Cisplatin
  • Fluorouracil
  • multidrug resistance-associated protein 1