Fig.4 Preoperative metformin administration reduces proliferative activity and alters cell proliferation signaling.

(A) Preoperative metformin administration decreased immunostaining of Ki-67 and topoisomerase IIα in endometrial cancer tissues. Representative changes in immunostaining are shown for paired specimens. The change in labeling indices, expressed as a percentage of positively stained nuclei among a total of 500 nuclei, are shown for each pair and evaluated using the Wilcoxon signed-rank test.
(B) Cell signaling molecules in endometrial cancer tissues were detected by western blotting, quantitated by densitometry, and normalized to β-actin. Pre: before the commencement of metformin treatment; Post: after metformin treatment. From Mitsuhashi et al., modified with permission^［21］