Gene expression profiles with cDNA microarray reveal RhoGDI as a predictive marker for paclitaxel resistance in ovarian cancers

Abstract

Abstract. In the current study, we identified paclitaxelresistant related genes by comparing gene expression profiles of paclitaxel-resistant and parent ovarian cancer cell lines. Gene expression profiles of the human ovarian cancer cell line (KF28), cisplatin-resistant cell line (KFr13) induced from KF28, and paclitaxel-resistant cell lines (KF28TX and KFr13TX) induced by exposing KF28 and KFr13 to doseescalating paclitaxel were compared and analyzed using cDNA microarray. Of 557 human cancer-related cDNA transcripts compared, 5 genes were found to be underexpressed and 5 genes overexpressed in the paclitaxelresistant KF28TX, while another paclitaxel-resistant KFr13TX had 5 underexpressed and 8 overexpressed genes. Among these genes, overexpression of the ATP-binding cassette subfamily (MDR-1), Rho guanine dinucleotide phosphate dissociation inhibitor beta (RhoGDI) and insulin-like growth factor binding protein 3 (IGFBP-3) was observed in both paclitaxel-resistant cell lines. Using real-time quantitative PCR, we confirmed the array results. We therefore conclude that IGFBP-3, RhoGDI and MDR-1 were correlated with paclitaxel resistance. Moreover, immunohistochemical staining was analyzed in 22 serous ovarian cancer tissues from patients who received paclitaxel-based chemotherapy, and RhoGDI overexpression was observed more frequently in non-responsers than in responders (p=0.004). RhoGDI expression proved to be a predictive marker of paclitaxel resistance not only in paclitaxel-resistant cell lines, but also in clinical samples.

The involvement of FOXO1 in cytotoxic stress and drug-resistance induced by paclitaxel in ovarian cancers

“…MDR-1 overexpression in ovarian cancer cell lines with paclitaxel resistance had been reported (Masanek et al, 1997;Duan et al, 1999). Similarly, we had also confirmed MDR-1 overexpression in paclitaxel-resistant derivative ovarian cancer cell line, KFr13 TX cells (Yamamoto et al, 2000b;Goto et al, 2006). The molecular mechanism of MDR-1 is still uncertain.…”

RhoGDI2 confers resistance to 5-fluorouracil in human gastric cancer cells

“…In addition, gastric cancer cells isolated from patients with higher levels of RhoGDI2 were more resistant to 5-FU. Other groups have shown that RhoGDI2 was overexpressed in chemotherapy-resistant fibrosarcoma cells and paclitaxel-resistant ovarian cancers, respectively (16,17). However, Lee et al (18) recently revealed contradictory results suggesting that the chemo-resistance in ovarian serous carcinomas is associated with the downregulation of RhoGDI2 expression.…”

Use of arrays to investigate the contribution of ATP-binding cassette transporters to drug resistance in cancer chemotherapy and prediction of chemosensitivity

“…Interestingly, the expression of ABCC3 and ABCC4 was decreased in the drug resistant cell lines. In a similar study of ovarian cancer cell line KF28 TX resistant to paclitaxel using an IntelliGene microarray (Table 2) containing 557 human cancer-related cDNAs including ABCB1 and ABCC3, ABCB1 was also found to be overexpressed and likely contribute to paclitaxel resistance [20]. Similar to the Clontech Rat cDNA array (see above), the usefulness of these arrays in ABC transporter profiling, however, is also limited.…”