Galectin-3 may contribute to Cisplatin resistance in clear cell carcinoma of the ovary

Int J Gynecol Cancer. 2007 Sep-Oct;17(5):1040-6. doi: 10.1111/j.1525-1438.2007.00916.x. Epub 2007 Apr 12.

Abstract

Our previous findings suggested that lower cell proliferation of clear cell carcinoma (CCC) of the ovary may contribute to its resistance to chemotherapy. We conducted the present study to find the gene that regulates cell proliferation of CCC and to elucidate whether it contributes to cisplatin (CDDP) resistance. Complementary DNA microarray analysis revealed that the gene expression level of galectin-3 of CCC cell lines (KK, RMG-I, HAC-2) was over threefold higher than that of ovarian serous adenocarcinoma (SAC) cell lines (HRA, KF). S-phase fraction increased after knocking down galectin-3 using small interfering RNA in RMG-I, KK, and HAC-2 cells. The protein expression of p27 decreased after knocking down galectin-3. CDDP-induced apoptosis was increased after knocking down galectin-3, and this cytotoxic effect was canceled by roscovitine. Immunohistochemical staining showed that galectin-3 expression in tumors of 20 CCC was significantly more frequent than that of 20 SAC (70.0% vs 15.0%, P = 0.0004). The present study showed that the expression of galectin-3 in CCC might contribute to its lower cell proliferation and lead to CDDP resistance.

MeSH terms

  • Adenocarcinoma, Clear Cell / chemistry
  • Adenocarcinoma, Clear Cell / drug therapy
  • Adenocarcinoma, Clear Cell / metabolism*
  • Antineoplastic Agents / therapeutic use
  • Apoptosis
  • Cell Line, Tumor
  • Cisplatin / therapeutic use
  • Cyclin-Dependent Kinase Inhibitor p27 / genetics
  • Cyclin-Dependent Kinase Inhibitor p27 / metabolism
  • Drug Resistance, Neoplasm / genetics*
  • Female
  • Galectin 3 / analysis
  • Galectin 3 / genetics
  • Galectin 3 / physiology*
  • Humans
  • Immunohistochemistry
  • Ovarian Neoplasms / chemistry
  • Ovarian Neoplasms / drug therapy
  • Ovarian Neoplasms / metabolism*
  • RNA, Small Interfering / pharmacology

Substances

  • Antineoplastic Agents
  • Galectin 3
  • RNA, Small Interfering
  • Cyclin-Dependent Kinase Inhibitor p27
  • Cisplatin