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Metformin Reduces Tumor Growth in a Murine Flank Schwannoma Model
Sudhir Manickavel1, Yolanda Hartman1, Andrew Burns1
1Department of Otolaryngology-Head and Neck Surgery, University of Alabama at Birmingham, Birmingham, Alabama.
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 mm 3 /day for saline compared with 73.7 ± 29.5 mm 3 /day for low-dose metformin ( p = 0.03) and 68.7 ± 34.8 mm 3 /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.
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