Axl downstream targeting unravels synergistic drug combinations in ovarian carcinoma cells

Desirè M. Alampi, Emilio Ciusani, Nives Carenini, Elisabetta Corna, Laura Gatti, Cristina Corno

Research output: Contribution to journalArticle

Abstract

Background: Platinum-based therapy represents the main pharmacological treatment for ovarian carcinoma. Since molecular targeting of receptor tyrosine kinases (RTK) affects factors that may modulate drug response, the aim of this study was to examine whether downstream targets of AXL RTK could be exploited to improve cell response to cisplatin. Materials and Methods: Inhibitors of p38 (SB203580) and of signal transducer and activator of transcription 3 (stattic) were employed in combination with cisplatin in ovarian carcinoma cell lines. Apoptosis assay and western blot analysis were performed to evaluate cell response after treatment. Results: SB203580 produced a synergistic effect in combination with cisplatin in cisplatin-resistant IGROV-1/Pt1 cells. In addition, a favorable drug interaction was observed in A2780 cells when pre-incubated with cisplatin prior to stattic. The analysis of cell response after combined treatment showed down-regulation of the pro-apoptotic protein BCL2-associated agonist of cell death (BAD). Conclusion: Our results support the notion that downstream targets of AXL in ovarian carcinoma cells can be exploited to increase cisplatin activity in ovarian carcinoma models.

Original languageEnglish
Pages (from-to)3803-3808
Number of pages6
JournalAnticancer Research
Volume39
Issue number7
DOIs
Publication statusPublished - Jan 1 2019

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Drug Combinations
Cisplatin
Carcinoma
Receptor Protein-Tyrosine Kinases
STAT3 Transcription Factor
Apoptosis Regulatory Proteins
Platinum
Drug Interactions
Cell Death
Down-Regulation
Western Blotting
Pharmacology
Apoptosis
Cell Line
Pharmaceutical Preparations

Keywords

  • AXL
  • Cisplatin
  • Ovarian carcinoma
  • P38 MAPK

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Axl downstream targeting unravels synergistic drug combinations in ovarian carcinoma cells. / Alampi, Desirè M.; Ciusani, Emilio; Carenini, Nives; Corna, Elisabetta; Gatti, Laura; Corno, Cristina.

In: Anticancer Research, Vol. 39, No. 7, 01.01.2019, p. 3803-3808.

Research output: Contribution to journalArticle

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AU - Gatti, Laura

AU - Corno, Cristina

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