Fig. 8

Schematic diagram of antitumor effect in vivo and in vitro and the proposed signaling pathway induced by combination treatment with d-borneol and CDDP. d-Borneol enhanced the sensitivity of CDDP by increasing CDDP cellular accumulation via inhibiting P-gp function. On the one hand, d-borneol enhanced p21 and p27 and suppressed two complexes, i.e., CDK2–cyclin A and CDK6–cyclin D, which blocked the cell cycle in S phase. On the other hand, d-borneol enhanced the sensitivity of CDDP to H460/CDDP cells by promoting the mitochondrially mediated intrinsic apoptosis via activating pro-apoptotic Bax, downregulating anti-apoptotic Bcl-2, and finally promoting activation of caspase-3, which leads to apoptosis. “←” indicates activation, and “⟝” indicates inhibition