Related Experiment Video

Updated: May 1, 2026

Establishing Dual Resistance to EGFR-TKI and MET-TKI in Lung Adenocarcinoma Cells In Vitro with a 2-step Dose-escalation Procedure
09:38

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

8.0K

Cepharanthine Reverses Gefitinib Resistance in NSCLC by Concurrently Inhibiting AKT/P70S6K Survival Signaling and

Li-Ping Kang1, Hui-Hui Chen1, Tong-Tong Lv1

  • 1Zhuhai Hospital of Integrated Traditional Chinese and Western Medicine, Zhuhai, Guangdong, China.

Chemical Biology & Drug Design
|April 30, 2026
PubMed

Insights

Cepharanthine (CEP) overcomes resistance to Epidermal Growth Factor Receptor (EGFR) tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC). CEP suppresses survival pathways and activates the STING immune pathway, enhancing TKI therapy.

Area of Science:

  • Oncology
  • Immunology
  • Pharmacology

Background:

  • Acquired resistance to EGFR TKIs presents a significant challenge in treating EGFR-mutant NSCLC.
  • Curing cancer patients with EGFR-mutant NSCLC who have acquired resistance to TKIs is a major therapeutic challenge.

Purpose of the Study:

  • To investigate the potential of cepharanthine (CEP) in overcoming gefitinib resistance in EGFR-mutant NSCLC.
  • To elucidate the underlying mechanisms of CEP's action, including its effects on survival pathways and innate immunity.

Main Methods:

  • Utilized gefitinib-resistant H1975 cells (EGFR L858R/T790M) for in vitro studies.
  • Assessed CEP's effects on cell proliferation, apoptosis, and key signaling pathways (AKT/P70S6K, STING).
  • Performed RNA sequencing and functional validation, including using a STING inhibitor (H-151).

Main Results:

  • CEP monotherapy inhibited proliferation and induced apoptosis in resistant cells.
  • CEP synergized with gefitinib to enhance anti-cancer effects.
  • CEP activated the STING/TBK1/IRF3 pathway, leading to increased production of T-cell chemoattractants (CXCL9, CXCL10, CCL5).
  • STING inhibition abrogated CEP's anti-tumor effects in vitro.

Conclusions:

  • Cepharanthine exhibits a novel dual mechanism of action against TKI-resistant NSCLC.
  • CEP suppresses the AKT/P70S6K survival axis and activates STING-mediated immunity.
  • CEP is a promising candidate for overcoming TKI resistance in NSCLC.
Keywords:
AKT/P70S6K pathwaySTING/TBK1/IRF3 pathwayapoptosiscepharanthinegefitinib resistancenon‐small cell lung cancer

More Related Videos

Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts10:27

Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts

Published on: July 25, 2020

6.5K
Development and Maintenance of a Preclinical Patient Derived Tumor Xenograft Model for the Investigation of Novel Anti-Cancer Therapies09:29

Development and Maintenance of a Preclinical Patient Derived Tumor Xenograft Model for the Investigation of Novel Anti-Cancer Therapies

Published on: September 30, 2016

13.4K

Related Concept Videos

Chemotherapy-Induced Nausea and Vomiting: Neurokinin-1 Receptor Antagonists01:28

Chemotherapy-Induced Nausea and Vomiting: Neurokinin-1 Receptor Antagonists

Neurokinin 1 (NK1) receptors are distributed across the GI tract, vagal afferents, and key CNS regions including the central vomiting center and chemoreceptor trigger zone (CTZ) Chemotherapy agents stimulate enterochromaffin cells in the gastrointestinal (GI) tract to release large amounts of substance P (SP). SP is a neuropeptide released by specific sensory nerves in response to many different stressors, including those in the GI mucosa affected by chemotherapy.  SP binds and activates...
820
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...
7.0K
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...
4.9K
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...
6.3K
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
4.8K
Tumor Immunotherapy01:27

Tumor Immunotherapy

Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.
2.5K