TITLE

Global gene expression analysis of early response to chemotherapy treatment in ovarian cancer spheroids

AUTHOR(S)
L'Espérance, Sylvain; Bachvarova, Magdalena; Tetu, Bernard; Mes-Masson, Anne-Marie; Bachvarov, Dimcho
PUB. DATE
January 2008
SOURCE
BMC Genomics;2008, Vol. 9, Special section p1
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Background: Chemotherapy (CT) resistance in ovarian cancer (OC) is broad and encompasses diverse unrelated drugs, suggesting more than one mechanism of resistance. To better understand the molecular mechanisms controlling the immediate response of OC cells to CT exposure, we have performed gene expression profiling in spheroid cultures derived from six OC cell lines (OVCAR3, SKOV3, TOV-112, TOV-21, OV-90 and TOV-155), following treatment with 10,0 µM cisplatin, 2,5 µM paclitaxel or 5,0 µM topotecan for 72 hours. Results: Exposure of OC spheroids to these CT drugs resulted in differential expression of genes associated with cell growth and proliferation, cellular assembly and organization, cell death, cell cycle control and cell signaling. Genes, functionally involved in DNA repair, DNA replication and cell cycle arrest were mostly overexpressed, while genes implicated in metabolism (especially lipid metabolism), signal transduction, immune and inflammatory response, transport, transcription regulation and protein biosynthesis, were commonly suppressed following all treatments. Cisplatin and topotecan treatments triggered similar alterations in gene and pathway expression patterns, while paclitaxel action was mainly associated with induction of genes and pathways linked to cellular assembly and organization (including numerous tubulin genes), cell death and protein synthesis. The microarray data were further confirmed by pathway and network analyses. Conclusion: Most alterations in gene expression were directly related to mechanisms of the cytotoxics actions in OC spheroids. However, the induction of genes linked to mechanisms of DNA replication and repair in cisplatin- and topotecan-treated OC spheroids could be associated with immediate adaptive response to treatment. Similarly, overexpression of different tubulin genes upon exposure to paclitaxel could represent an early compensatory effect to this drug action. Finally, multicellular growth conditions that are known to alter gene expression (including cell adhesion and cytoskeleton organization), could substantially contribute in reducing the initial effectiveness of CT drugs in OC spheroids. Results described in this study underscore the potential of the microarray technology for unraveling the complex mechanisms of CT drugs actions in OC spheroids and early cellular response to treatment.
ACCESSION #
38123111

 

Related Articles

  • Nucleoside transporters are widely expressed in ovarian carcinoma effusions. Bock, Annika; Dong, Hiep; Tropé, Claes; Staff, Anne; Risberg, Björn; Davidson, Ben // Cancer Chemotherapy & Pharmacology;Feb2012, Vol. 69 Issue 2, p467 

    Objective: Equilibrative and concentrative nucleoside transporters (ENTs and CNTs) mediate the cellular uptake of anticancer nucleosides and sensitivity to such compounds. We studied the expression of ENTs and CNTs in ovarian carcinoma effusions. Methods: ENT1, ENT2, ENT4 and CNT3 expression was...

  • Epithelial membrane protein 1 expression in ovarian serous tumors. DEMIRAG, GUZIN GONULLU; KEFELI, MEHMET; KEMAL, YASEMIN; YUCEL, IDRIS // Oncology Letters;Mar2016, Vol. 11 Issue 3, p2140 

    The present study aimed to analyze the clinical significance of epithelial membrane protein 1 (EMP1) expression in ovarian serous tumors. A total of 84 cases of ovarian serous tumor (50 patients with malignant ovarian serous tumors and 34 patients with borderline and benign serous tumors) were...

  • Phase III Randomized Trial of Docetaxel—Carboplatin Versus Paclitaxel—Carboplatin as First-line Chemotherapy for Ovarian Carcinoma. Vasey, Paul A.; Jayson, Gordon C.; Gordon, Alan; Gabra, Hani; Coleman, Rob; Atkinson, Ronnie; Parkin, David; Paul, James; Hay, Andrea; Kaye, Stan B. // JNCI: Journal of the National Cancer Institute;11/17/2004, Vol. 96 Issue 22, p1682 

    Background: Chemotherapy with a platinum agent and a taxane (paclitaxel) is considered the standard of care for treatment of ovarian carcinoma. We compared the combination of docetaxel-carboplatin with the combination of paclitaxel-carboplatin as first-line chemotherapy for stage Ic-IV...

  • Profile of trebananib (AMG386) and its potential in the treatment of ovarian cancer. Liontos, Michalis; Lykka, Maria; Meletios-Athanasios; Dimopoulos; Bamias, Aristotle // OncoTargets & Therapy;2014, Vol. 7, p1837 

    Angiogenesis has been implicated in ovarian cancer pathogenesis. Bevacizumab, an anti-vascular endothelial growth factor monoclonal antibody, has recently been incorporated in ovarian cancer treatment in combination with chemotherapy both in a frontline setting and in disease recurrence....

  • Telik Cancer Study Misses Mark Following Halt in Recruitment. Hollingsworth, Catherine // BioWorld Today;10/31/2008, Vol. 19 Issue 213, p1 

    The article reports on the decision by Palo Alto, California-based Telik Inc. to stop enrolling patients in a Phase III study of drug candidate Telcyta for ovarian cancer due to the interruption of a five-month clinical hold. The strength of the study has been negatively affected by the move,...

  • paclitaxel.  // Royal Society of Medicine: Medicines;2002, p421 

    The article presents information on paclitaxel, a cytotoxic drug, the first of a new group of drugs termed the taxanes. It is used as an anticancer drug in the treatment of ovarian and breast cancer, and also non-small cell lung cancer. Administration is by intravenous infusion.

  • Individualizing Care for Ovarian Cancer Patients Using Big Data. Fridley, Brooke L.; Koeslter, Devin C.; Godwin, Andrew K. // JNCI: Journal of the National Cancer Institute;May2014, Vol. 106 Issue 5, p1 

    The authors discuss two articles published in the current issue of the journal which tackle the use of big data for individualizing care for ovarian cancer patients. They examine several important aspects of the articles including the representation of the largest sample size utilized in the...

  • Mathematical Prognostic Biomarker Models for Treatment Response and Survival in Epithelial Ovarian Cancer. Nikas, Jason B.; Boylan, Kristin L. M.; Skubitz, Amy P. N.; Low, Walter C. // Cancer Informatics;2011, Issue 9, p233 

    Following initial standard chemotherapy (platinum/taxol), more than 75% of those patients with advanced stage epithelial ovarian cancer (EOC) experience a recurrence. There are currently no accurate prognostic tests that, at the time of the diagnosis/surgery, can identify those patients with...

  • High-temperature-required protein A2 as a predictive marker for response to chemotherapy and prognosis in patients with high-grade serous ovarian cancers. Miyamoto, M; Takano, M; Iwaya, K; Shinomiya, N; Goto, T; Kato, M; Suzuki, A; Aoyama, T; Hirata, J; Nagaoka, I; Tsuda, H; Furuya, K // British Journal of Cancer;2/17/2015, Vol. 112 Issue 4, p739 

    Background:High-temperature-required protein A2 (HtrA2), a protein relating with apoptosis in a caspases-dependent and non-dependent manner, has been reported to be associated with chemosensitivity in several human cancers.Methods:Tissue microarrays made from 142 patients with high-grade serous...

Share

Other Topics