The Src inhibitor AZD0530 blocks invasion and may act as a radiosensitizer in lung cancer cells

Purnell, Phillip R; Mack, Philip C; Tepper, Clifford G; Evans, Christopher P; Green, Tim P; Gumerlock, Paul H; Lara, Primo N; Gandara, David R; Kung, Hsing-Jien; Gautschi, Oliver (2009). The Src inhibitor AZD0530 blocks invasion and may act as a radiosensitizer in lung cancer cells. Journal of thoracic oncology, 4(4), pp. 448-54. Hagerstown, Md.: Wolters Kluwer Health/Lippincott Williams & Wilkins 10.1097/JTO.0b013e31819c78fb

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BACKGROUND: With the emergence of Src inhibitors in clinical trials, improved knowledge of the molecular responses of cancer cells to these agents is warranted. This will facilitate the development of tests to identify patients who may benefit from these agents, allow drug activity to be monitored and rationalize the combination of these agents with other treatment modalities. METHODS: This study evaluated the molecular and functional effects of Src inhibitor AZD0530 in human lung cancer cells, by Western blotting and reverse transcription-polymerase chain reaction, and by assays for cell viability, migration, and invasion. RESULTS: Src was activated in four of five cell lines tested and the level corresponded with the invasive potential and the histologic subtype. Clinically relevant, submicromolar concentrations of AZD0530 blocked Src and focal adhesion kinase, resulting in significant inhibition of cell migration and Matrigel invasion. Reactivation of STAT3 and up-regulation of JAK indicated a potential mechanism of resistance. AZD0530 gave a potent and sustained blockage of AKT and enhanced the sensitivity to irradiation. CONCLUSIONS: The results indicated that AZD0530, aside from being a potent inhibitor of tumor cell invasion which could translate to inhibition of disease progression in the clinic, may also lower resistance of lung cancer cells to pro-apoptotic signals.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Medical Oncology

UniBE Contributor:

Gautschi, Oliver

ISSN:

1556-0864

Publisher:

Wolters Kluwer Health/Lippincott Williams & Wilkins

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 15:11

Last Modified:

04 May 2014 23:22

Publisher DOI:

10.1097/JTO.0b013e31819c78fb

PubMed ID:

19240653

Web of Science ID:

000264611100003

URI:

https://boris.unibe.ch/id/eprint/31378 (FactScience: 195872)

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