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Updated: Jan 27, 2026

Establishment of Gastric Cancer Patient-derived Xenograft Models and Primary Cell Lines
Published on: July 19, 2019
Methylxanthine derivatives promote autophagy in gastric cancer cells targeting PTEN
Hanyang Liu1, Jun Song, Yan Zhou
1Department of Gastrointestinal Surgery, The Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University, Changzhou, Jiangsu Province, China.
Abstract:
Methylxanthine derivatives, such as caffeine and theophylline, enhance cell apoptosis and autophagy and reportedly induce the activity of phosphatase and tensin homologue (PTEN) and inhibit the mammalian target of rapamycin (mTOR). This study investigated the impacts of caffeine and theophylline on gastric cancer cell apoptosis and autophagy using a gastric cancer cell line (MGC-803) and a nude mouse model. Peritumoural and tumour tissues were collected from five patients diagnosed with gastric carcinoma who underwent laparoscopic radical gastrectomy at our hospital. Autophagy was suppressed in gastric cancer tumour tissue compared with peritumoural tissue. In vitro, both caffeine and theophylline effectively suppressed MGC-803 cell proliferation and migration and induced autophagy. To assess the involvement of PTEN in caffeine-mediated and theophylline-mediated gastric cancer cell death, we transiently transfected MGC-803 cells with an siRNA targeting PTEN. PTEN knockdown impaired the methylxanthine derivative-mediated inhibition of PI3K/Akt/mTOR signalling. In nude mice treated with caffeine or theophylline, MGC-803 cell tumours injected with siPTEN were larger than those injected with negative control siRNA. These results show that the methylxanthine derivatives (caffeine and theophylline) effectively induce gastric cancer cell apoptosis and autophagy by PTEN activation and PI3K/Akt/mTOR pathway suppression and strongly support the use of methylxanthine derivatives as potential anticancer therapeutics.
Insights
Caffeine and theophylline, methylxanthine derivatives, promote gastric cancer cell death by increasing apoptosis and autophagy. These compounds activate phosphatase and tensin homologue (PTEN), inhibiting the PI3K/Akt/mTOR pathway.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Gastric cancer exhibits suppressed autophagy in tumor tissues compared to adjacent normal tissues.
- Methylxanthine derivatives like caffeine and theophylline are known to influence apoptosis and autophagy.
- These compounds reportedly modulate phosphatase and tensin homologue (PTEN) activity and mammalian target of rapamycin (mTOR) signaling.
Purpose of the Study:
- To investigate the effects of caffeine and theophylline on gastric cancer cell apoptosis and autophagy.
- To elucidate the role of PTEN in methylxanthine derivative-induced gastric cancer cell death.
- To evaluate the therapeutic potential of caffeine and theophylline in a gastric cancer model.
Main Methods:
- Utilized the MGC-803 gastric cancer cell line and a nude mouse model.
- Assessed apoptosis and autophagy in vitro and in vivo.
- Employed PTEN knockdown via siRNA transfection to examine pathway involvement.
- Monitored tumor growth in nude mice treated with methylxanthines and PTEN siRNA.
Main Results:
- Caffeine and theophylline suppressed MGC-803 cell proliferation and migration while inducing autophagy.
- PTEN knockdown reversed the inhibitory effects of methylxanthines on the PI3K/Akt/mTOR pathway.
- Tumor growth was significantly larger in mice treated with PTEN siRNA compared to controls when administered methylxanthines.
Conclusions:
- Methylxanthine derivatives (caffeine and theophylline) induce gastric cancer cell apoptosis and autophagy.
- These effects are mediated through PTEN activation and subsequent PI3K/Akt/mTOR pathway suppression.
- Caffeine and theophylline show promise as potential anticancer therapeutics for gastric cancer.
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