12P - Cigarette smoke promotes proliferation of non-small cell lung cancer (NSCLC) via enhancing glucose uptake and glycolysis
- I-Shan Hsieh (TW)
- Fang-Ju Cheng (TW)
- Chih-Yen Tu (TW)
- Chia-Hung Chen (TW)
- Te-Chun Hsia (TW)
- Bo-Wei Wang (TW)
- Yi-Lun Yeh (TW)
- Wei-Chien Huang (TW)
- I-Shan Hsieh (TW)
Abstract
Background
Cigarette smoking has been demonstrated as an important risk factor for lung cancer and causes poor prognosis. The critical roles of aerobic glycolysis and Warburg effect in supplying building blocks and energy for proliferation of lung cancer cells have also been well documented. However, it still remains unclear whether and how cigarette smoke alters the glucose uptake and glucose metabolism to promote the proliferation of NSCLC.
Methods
Glycolysis and mitochondrial respiration rate were quantified by Seahorse XF analyzer. The gene expressions were assessed by quantitative RT-PCR and immunoblot. The cell lines were manipulated to inhibit or knockdown glucose transporters by glucose transporter competitive inhibitors and si-RNA. Fluorescence–labeled glucose analogue was employed to measure the glucose uptake ability. Cell viability and proliferation rate were analyzed by MTT assay and IncuCyte live cell analysis system respectively. Biochemical assays were used to evaluate the levels of glycolytic products.
Results
NSCLC A549 and NCI-H292 cell lines were treated with cigarette smoke extract (CSE) or its carcinogenic ingredient Benzo[α]pyrene (B[α]P) as the cigarette smoke exposure models. Cigarette smoke promoted glucose uptake and glucose metabolism in NSCLC by increasing glucose transporter 3 (GLUT3) and sodium glucose transporter 1 (SGLT1) expression. The enhancing glycolysis activity was demonstrated in 13C labelling LC/MS detection and further confirmed in biochemical assays of endogenous lactate and NADH production. Inhibiting glucose transporters were related to promoting survival in cigarette smoke treated cancer cells.
Conclusions
The results suggest that targeting glucose transporters or glucose metabolism related enzymes in combination with the standard treatment are potential therapeutic strategies in treating smoker lung cancer patients.
Clinical trial identification
NA
Legal entity responsible for the study
China Medical University, Taiwan
Funding
Ministry of Science and Technology, Taiwan
Disclosure
All authors have declared no conflicts of interest.
