The Effects of Different mTOR Inhibitors in EGFR Inhibitor Resistant Colon Carcinoma Cells

Tamás Sticz, Anna Molnár, Titanilla Dankó, Zoltán Hujber, Gábor Petővári, Noémi Nagy, Gyula Végső, L. Kópper, A. Sebestyén

Research output: Article

3 Citations (Scopus)

Abstract

Several monoclonal antibodies and inhibitors targeting signalling pathways are being used in personalised medicine. Anti-EGFR antibodies seem to be effective, however, therapy resistance often occurs in colon carcinoma cases. mTOR inhibitors (mTORIs) could have a potential role in the breakthrough of therapy resistance. The mTOR activity related protein expression patterns and the in vitro effects of EGFR inhibitors (EGFRIs), mTORIs and their combinations were studied in different colon carcinoma cell lines (with different genetic backgrounds). Alamar Blue test and flow cytometry were used to analyse the in vitro proliferation and apoptotic effects of cetuximab, gefitinib, cisplatin, rapamycin, PP242 and NVP-BEZ235. The expressions of mTOR activity related proteins (p-70S6K, p-S6, Rictor, p-mTOR, Raptor) were studied by Western blot, immunocytochemistry and Duolink staining. The EGFRI resistance of the studied colon carcinoma cell lines related to their known mutations were confirmed, neither gefitinib nor cetuximab inhibited the proliferation or induced apoptosis in vitro. Individual differences in Rictor and Raptor expressions were detected by Western blot and immunocytochemistry beside elevated mTOR activity of these different colon carcinoma cell lines. These expression patterns correlated to the mTORIs sensitivity differences, moreover, mTORIs could enhance the effects of EGFRIs and other in vitro treatments. Our results suggest that mTORI combinations could be helpful in both EGFRI and platinum-based therapy of colon carcinomas. Moreover, we suggest determining both mTOR complex activity and mutations in Akt/mTOR signalling pathways for selecting the appropriate mTORIs and patients in potential future combination treatments.

Original languageEnglish
Pages (from-to)1-8
Number of pages8
JournalPathology and Oncology Research
DOIs
Publication statusAccepted/In press - jún. 7 2018

Fingerprint

Colon
Carcinoma
Raptors
Cell Line
Western Blotting
Immunohistochemistry
Therapeutics
S 6
Precision Medicine
Mutation
Sirolimus
Platinum
Individuality
Cisplatin
Anti-Idiotypic Antibodies
Flow Cytometry
Proteins
Monoclonal Antibodies
Apoptosis
Staining and Labeling

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Oncology
  • Cancer Research

Cite this

The Effects of Different mTOR Inhibitors in EGFR Inhibitor Resistant Colon Carcinoma Cells. / Sticz, Tamás; Molnár, Anna; Dankó, Titanilla; Hujber, Zoltán; Petővári, Gábor; Nagy, Noémi; Végső, Gyula; Kópper, L.; Sebestyén, A.

In: Pathology and Oncology Research, 07.06.2018, p. 1-8.

Research output: Article

Sticz, Tamás ; Molnár, Anna ; Dankó, Titanilla ; Hujber, Zoltán ; Petővári, Gábor ; Nagy, Noémi ; Végső, Gyula ; Kópper, L. ; Sebestyén, A. / The Effects of Different mTOR Inhibitors in EGFR Inhibitor Resistant Colon Carcinoma Cells. In: Pathology and Oncology Research. 2018 ; pp. 1-8.
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