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RT-PCR showed strong suppression of BCL-2 but induction of BAX and PTEN. Prolonged shikonin treatment caused a total loss of the nuclear membrane, whereas metformin prevented this damage while promoting apoptotic morphologies. Our real-time PCR detected reduced levels of EMT genes but increases in the anti-EMT geneCDH1. Combined treatment also reduced CD44/CD24 ratios in favor of chemosensitivity. Binding energies strongly favored shikonin interactions with growth-signaling molecules. Shikonin and metformin synergize in inhibiting the
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