Related Experiment Video

Updated: May 15, 2026

Establishment and Characterization of Three Afatinib-resistant Lung Adenocarcinoma PC-9 Cell Lines Developed with Increasing Doses of Afatinib
09:38

Establishment and Characterization of Three Afatinib-resistant Lung Adenocarcinoma PC-9 Cell Lines Developed with Increasing Doses of Afatinib

Published on: June 26, 2019

Gefitinib-resistance is related to BIM expression in non-small cell lung cancer cell lines

Heyan Li1, Songwen Zhou, Xuefei Li

  • 1Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.

Cancer Biotherapy & Radiopharmaceuticals
|December 29, 2012
PubMed

Insights

Gefitinib resistance in non-small cell lung cancer (NSCLC) can be overcome by combining PI3K and MEK inhibitors. This combination therapy restores Gefitinib sensitivity by increasing BIM expression and inducing apoptosis.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Epidermal growth factor receptor (EGFR) signaling pathways, including PI3K/AKT and MEK/ERK, are crucial in non-small cell lung cancer (NSCLC) sensitive to Gefitinib.
  • Acquired resistance to Gefitinib in NSCLC is often mediated by the activation of these downstream PI3K/AKT or MEK/ERK pathways.

Purpose of the Study:

  • To investigate therapeutic strategies for overcoming Gefitinib resistance in non-small cell lung cancer.
  • To explore the role of the proapoptotic protein BIM in Gefitinib sensitivity and resistance.
  • To evaluate the efficacy of combining PI3K and MEK inhibitors to restore Gefitinib sensitivity.

Main Methods:

  • Utilized Gefitinib-sensitive NSCLC cell lines.
  • Investigated the effect of Gefitinib on tumor cell apoptosis and BIM expression.
  • Employed small interfering RNA (siRNA) to silence BIM and assess its impact on apoptosis.
  • Administered a combination therapy of PI3K inhibitor (LY294002) and MEK inhibitor (U0126) to resistant cell lines.

Main Results:

  • Gefitinib induced apoptosis in sensitive NSCLC cells through BIM upregulation.
  • Silencing BIM expression attenuated Gefitinib-induced apoptosis.
  • Combination therapy with PI3K and MEK inhibitors significantly induced apoptosis in resistant cells.
  • The combined treatment restored sensitivity to Gefitinib by enhancing BIM expression.

Conclusions:

  • The PI3K/AKT and MEK/ERK pathways play a critical role in Gefitinib resistance in NSCLC.
  • Targeting BIM is a potential strategy to enhance Gefitinib efficacy.
  • Combination therapy involving PI3K and MEK inhibitors offers a promising approach to overcome Gefitinib resistance in NSCLC by modulating BIM expression.

More Related Videos

Establishing Dual Resistance to EGFR-TKI and MET-TKI in Lung Adenocarcinoma Cells In Vitro with a 2-step Dose-escalation Procedure09:38

Establishing Dual Resistance to EGFR-TKI and MET-TKI in Lung Adenocarcinoma Cells In Vitro with a 2-step Dose-escalation Procedure

Published on: August 11, 2017

A Combined 3D Tissue Engineered In Vitro/In Silico Lung Tumor Model for Predicting Drug Effectiveness in Specific Mutational Backgrounds13:34

A Combined 3D Tissue Engineered In Vitro/In Silico Lung Tumor Model for Predicting Drug Effectiveness in Specific Mutational Backgrounds

Published on: April 6, 2016

Related Concept Videos

Treatment Resistant Cancers02:56

Treatment Resistant Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against specific...
Combination Therapies and Personalized Medicine02:50

Combination Therapies and Personalized Medicine

Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...