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. Author manuscript; available in PMC: 2022 May 4.
Published in final edited form as: Cell Metab. 2021 Feb 19;33(5):1013–1026.e6. doi: 10.1016/j.cmet.2021.02.001

Figure 5. Combining metformin with asparaginase impairs tumor growth.

Figure 5.

(A) Endpoint tumor volume (mm3) (day 26 of treatment) of A549 subcutaneous tumor xenografts in mice treated with metformin (250 mg/kg/day), asparaginase (ASNase) (5 IU/kg), the combination, or vehicle controls as determined by caliper measurements (n = 9-10).

(B) A549 tumor xenograft growth curves from metformin/asparaginase treatment start date through endpoint.

(C) Endpoint tumor volume (mm3) (day 21 of treatment) of SUM159PT subcutaneous tumor xenografts in mice treated with metformin (250 mg/kg/day), asparaginase (ASNase) (5 IU/kg), the combination, or vehicle controls as determined by caliper measurements. n = 7-10.

(D) Endpoint tumor mass of KPC-7940B orthotopic tumors treated with phenformin (1.7mg/mL), asparaginase (ASNase) (2 IU), the combination, or vehicle controls. n = 5-6.

(E) Immunoblot of lysates from metformin/asparaginase-treated A549 tumor xenografts shown in (A-B). Lysates were immunoblotted for mTORC1 activation marker phospho-Ser235/6 S6, total S6K, total S6, phospho-Thr172 AMPK, total AMPK, ASNS, tubulin, and actin. The three middle-sized tumors of each treatment group were chosen as representatives. Data are mean +/− s.e.; P value determined by unpaired two-tailed t-test: *p<0.05; **p<0.01; ***p<0.001; ns, not significant. See also Figure S4.