Metformin Reduces Tumor Growth in a Murine Flank Schwannoma Model

Abstract

Hypothesis Metformin and aspirin reduce vestibular schwannoma (VS) growth. Background There have been reported associations between patients with VS prescribed metformin and decreased tumor volumetric growth. Aspirin has also been associated with decreased VS growth in animal studies. Methods Rat schwannoma cell lines were grown and implanted into 50 athymic nude mice. Tumors were grown to 5 mm, and then mice were injected with either low- or high-dose metformin, aspirin, or saline daily. Tumors were measured until 14 days elapsed or mice demonstrated symptoms such as ulceration, inability to walk, or passed away. Results There were no significant differences in day 0 tumor sizes between the control and the treatment groups (p = 0.73). In the low-dose, but not high-dose groups, day 7 volumes were significantly different for both metformin (p = 0.04) and aspirin (p = 0.02) compared with placebo. Mean tumor growth rates were 126.6 ± 65.6 mm3/day for saline compared with 73.7 ± 29.5 mm3/day for low-dose metformin (p = 0.03) and 68.7 ± 34.8 mm3/day for low-dose aspirin (p = 0.016). There were no significant differences in tumor sizes (p = 0.59) or growth rates (p = 0.75) between low-dose metformin and aspirin groups. Low-dose groups had treatment stopped at 14 days, with continued monitoring demonstrating significant increases in tumor growth off treatment for both aspirin (p = 0.006) and metformin (p = 0.048). Conclusions Metformin treatment significantly reduced VS growth to a similar level as aspirin. Furthermore, when removing both metformin and aspirin treatment, tumor growth significantly increased.