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Through the Looking Glass: Time-lapse Microscopy and Longitudinal Tracking of Single Cells to Study Anti-cancer Therapeutics
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Pazopanib restricts small cell lung cancer proliferation via reactive oxygen species-mediated endoplasmic reticulum

Yue Li1, Chen Chen1, Hai-Lin Liu1

  • 1Department of Lung Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin Lung Cancer Center, Tianjin, China.

Thoracic Cancer
|July 22, 2022
PubMed
Abstract

Insights

Pazopanib triggers apoptosis in small cell lung cancer (SCLC) cells by activating ER-stress and increasing reactive oxygen species (ROS). This study clarifies pazopanib

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Pazopanib is an approved anticancer agent for soft tissue sarcoma (STS) and renal cell carcinoma (RCC).
  • Its efficacy and mechanisms against small cell lung cancer (SCLC) are under investigation.
  • The precise anti-SCLC mechanisms of pazopanib remain unclear.

Purpose of the Study:

  • To elucidate the molecular mechanisms by which pazopanib exerts its anti-SCLC effects.
  • To investigate the role of endoplasmic reticulum (ER) stress and reactive oxygen species (ROS) in pazopanib-induced SCLC apoptosis.
  • To evaluate the in vivo efficacy of pazopanib in an SCLC xenograft model.

Main Methods:

  • Cell viability assays (CCK-8) and flow cytometry (Annexin V/PI staining) were used to assess apoptosis.
  • Western blot analysis detected apoptotic markers and ER-stress pathway proteins.
  • ROS levels were measured by flow cytometry, and an NCI-H446 xenograft model was used for in vivo studies.

Main Results:

  • Pazopanib inhibited SCLC cell proliferation and induced apoptosis, evidenced by increased cleaved-caspase3/Bax and decreased Bcl-2.
  • Pazopanib activated the PERK-related ER-stress pathway and increased intracellular ROS levels.
  • Inhibition of ER-stress or ROS reversed pazopanib-induced apoptosis in SCLC cells, and pazopanib suppressed tumor growth in vivo.

Conclusions:

  • Pazopanib induces SCLC cell apoptosis via ER-stress activation and ROS upregulation.
  • These findings provide mechanistic insights into pazopanib's anti-SCLC activity.
  • Further research into predictive biomarkers for pazopanib treatment in SCLC is warranted.
Keywords:
Pazopanibapoptosisendoplasmic reticulum stress (ER-stress)reactive oxygen species (ROS)small cell lung cancer (SCLC)

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