Investigation of the anticancer effects of Metformin in combination with 2-DG in small cell lung cancer

Pei-Yi Shih (施佩誼) 1, Mei-Chih Liang (梁美智) 1

1Department of Biological Science & Technology, National Yang Ming Chiao Tung University

Lung cancer is the leading cause of cancer mortality in global cancer statistics. Lung cancer is divided into small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC).Although SCLC only accounts for 15 percent of all lung cancers, SCLC has a high mortality rate due to its characteristics of rapid growth, rapid spread, early metastasis, and drug resistance.

At this stage, the FDA has approved the first-line chemotherapy as a combination of etoposide and cisplatin, called EP therapy, and the second-line chemotherapy is topotecan. Patients initially respond well to first-line chemotherapy, but most relapse after a few months and develop resistance. And second-line chemotherapy can not effectively improve the five-year survival rate.

Metformin is the first-line drug approved by the FDA to treat type 2 diabetes (T2D), but it has been found in other studies that metformin can inhibit cell growth and cellular protein synthesis by inhibiting the mTOR molecule. 2-DG is a glucose analog that blocks glycolysis by competing with glucose, thereby preventing cancer cells from obtaining energy.

By detecting cell viability, cell apoptosis, cell cycle distribution and signaling pathways, the anticancer effect of metformin combined with 2-DG on small cell lung cancer was studied. The study found that the combination of drugs can effectively inhibit the proliferation of cancer cells and induce their apoptosis, and also lead to more cell cycle accumulation in the sub-G1 phase. In addition, it can reduce the phosphorylation of S6 downstream of mTOR.

In summary, it was confirmed that both metformin and 2-DG alone have anticancer effects, but combined use can effectively increase the anticancer activity. Therefore, combination therapy has the opportunity to become a treatment option for patients with small cell lung cancer.