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Inhibitory effect of NVP-BKM120 on cholangiocarcinoma cell growth

Sureerat Padthaisong1,2, Hasaya Dokduang1,2,3, Supak Yothaisong1,2

  • 1Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.

Oncology Letters
|July 17, 2018
PubMed

Insights

NVP-BKM120, a phosphatidylinositol 3-kinase (PI3K) inhibitor, effectively reduced cholangiocarcinoma (CCA) cell growth and tumor progression in preclinical models. This PI3K inhibitor demonstrated anti-cancer effects without significant toxicity, suggesting its therapeutic potential for CCA treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Aberrant activation of the phosphatidylinositol 3-kinase (PI3K) pathway is implicated in various cancers, including cholangiocarcinoma (CCA).
  • Targeting the PI3K pathway presents a potential therapeutic strategy for CCA treatment.

Purpose of the Study:

  • To evaluate the efficacy of NVP-BKM120, a pan-class I PI3K inhibitor, in inhibiting CCA cell growth.
  • To assess the anti-tumor effects of NVP-BKM120 both *in vitro* and *in vivo*.

Main Methods:

  • Sulforhodamine B (SRB) assay to determine *in vitro* cell growth inhibition.
  • *In vivo* studies using CCA-inoculated nude mice treated with NVP-BKM120.
  • Immunohistochemical analysis for Ki67 expression and TUNEL assay for apoptosis.
  • Western blot analysis to investigate pathway modulation.

Main Results:

  • NVP-BKM120 significantly inhibited CCA cell growth in a dose-dependent manner *in vitro*.
  • Oral administration of NVP-BKM120 reduced tumor growth in CCA-inoculated mice, as evidenced by decreased Ki67 expression.
  • NVP-BKM120 induced cancer cell death (apoptosis) without observable toxicity in mice.
  • NVP-BKM120 suppressed RAC serine/threonine protein kinase/mechanistic target of rapamycin (mTOR) activation and inhibited phosphatase and tensin homolog (PTEN) phosphorylation.

Conclusions:

  • NVP-BKM120 exhibits potent anti-cancer activity against CCA by inhibiting key signaling pathways.
  • NVP-BKM120 demonstrates therapeutic potential as a treatment agent for cholangiocarcinoma.
Keywords:
NVP-BKM120Opisthorchis viverrinicholangiocarcinomaphosphatidylinositol 3-kinase pathway

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