New and Old Genes Associated with Primary and Established Responses to Paclitaxel Treatment in Ovarian Cancer Cell Lines

Abstract

Development of drug resistance is the main reason for low chemotherapy effectiveness in treating ovarian cancer. Paclitaxel (PAC) is a chemotherapeutic drug used in the treatment of this cancer. We analysed the development of PAC resistance in two ovarian cancer cell lines. Exposure of drug-sensitive cell lines (A2780 and W1) to PAC was used to determine the primary response. An established response was determined in PAC-resistant sublines of the A2780 and W1 cell lines. qRT-PCR was performed to measure the expression levels of specific genes. We observed decreased expression of the PCDH9, NSBP1, MCTP1 and SEMA3A genes in the PAC-resistant cell lines. Short-term exposure to PAC led to increased expression of the MDR1 and BCRP genes in the A2780 and W1 cell lines. In the A2780 cell line, we also observed increased expression of the C4orf18 gene and decreased expression of the PCDH9 and SEMA3A genes after PAC treatment. In the W1 cell line, short-term treatment with PAC upregulated the expression of the ALDH1A1 gene, a marker of Cancer stem cells (CSCs). Our results suggest that downregulation of the PCDH9, NSBP1, MCTP1 and SEMA3A genes and upregulation of the MDR1, BCRP, C4orf18 and ALDH1A1 genes may be related to PAC resistance.

The Significance of MicroRNAs Expression in Regulation of Extracellular Matrix and Other Drug Resistant Genes in Drug Resistant Ovarian Cancer Cell Lines

“…It is a tumor suppressor gene, and its downregulation correlates with progression of gastric [90] and ovarian cancer [91]. Recently, we described SEMA3A downregulation in three PAC-resistant ovarian cancer cell lines [92]. Here we showed that expression of SEMA3A can be influenced by miR-145 upregulation in the PAC resistant cell line.…”

“…It is a tumor suppressor gene with decreased expression in ovarian [99] and gastric cancer [100], and its downregulation usually correlates with disease progression and shorter survival. Previously, we observed the PCDH9 downregulation in three PAC resistant cell lines [92], suggesting its significance in resistance to this cytotoxic agent. However, there are no literature data available describing the regulation of the PCDH9 gene by miR-195 or miR-497.…”

The significance of microRNA genes expression in ovarian cancer cell lines resistant to cytotoxic drugs

“…It is a tumour suppressor gene with decreased expression in ovarian [104] and gastric cancer [105] and its downregulation usually correlates with disease progression and shorter survival. Previously we observed the PCDH9 downregulation in three PAC resistant cell lines [97] suggesting its significance in resistance to this cytotoxic agent. However, there are no literature data available describing the regulation of PCDH9 gene by miR-195 or miR-497.…”

“…It is a tumour suppressor gene and its downregulation correlates with progression of gastric [95] and ovarian cancer [96]. Recently we described SEMA3A downregulation in three PAC-resistant ovarian cancer cell lines [97].…”

Semaphorin 3A (SEMA3A), protocadherin 9 (PCdh9), and S100 calcium binding protein A3 (S100A3) as potential biomarkers of carcinogenesis and chemoresistance of different neoplasms, including ovarian cancer — review of literature

“…Semaphorin 3A (SEMA3A), protocadherin 9 (PCDH9), and S100 calcium binding protein A3 (S100A3) were discovered among the genes that exhibited changed expression and have not been previously associated with the development of drug resistance. The expression of all of these genes was shown to be altered in microarray-based studies conducted on ovarian cancer cell lines resistant to most commonly used cytotoxic drugs [11][12][13].…”