Fig 2: Anticancer molecular mechanism of metformin combined with everolimus in cervical cancer treatment. Metformin sensitizes everolimus, which mainly modulates MAPKs (p38, ERK, and JNK) upregulation and PI3K/AKT downregulation, activating or inactivating various signaling targets, such as Bax, Bcl2, caspase-3, PARP-1, Complex I, mtROS, p21, and p27. The activation and inactivation of these signaling pathways induced subG1- and G0/G1-phase arrest and caspase-dependent apoptosis, which increase the anticancer effects on cervical cancer.

Fig 3: Luteolin combined with asiatic acid induced apoptosis through inhibition of PI3K/AKT and regulation of MAPKs pathways in cervical cancer cells. Western blotting was used to detect PIK3CA, p-AKT, AKT, p-70S6K, 70S6K, p-p38, p38, p-ERK1/2, ERK1/2, p-JNK1/2 and JNK1/2 levels in CaSki (A) and HeLa (B) cells treated with Lut (50 µM) or AsA (50 µM) alone or in combination for 24 h. GAPDH served as the loading control. Quantitative results are shown in the lower plot. Values represent mean ± SD from three replicates. *, † and d p ? 0.05 compared with CON, L50- or A50-treated group. CON, 0.1% DMSO; L50, 50 µM luteolin; A50, 50 µM asiatic acid; Comb., 50 µM luteolin + 50 µM asiatic acid.

Fig 4: Schematic diagram of luteolin combined with asiatic acid’s anticancer molecular mechanism in cervical cancer. Lut combined with AsA mainly modulates FAK signaling (integrin ß1, paxillin and FAK) and PI3K/AKT signaling (PI3K, AKT and p70S6K) and causes JNK/p38 downregulation and ERK upregulation, inactivating or activating various signaling targets, such as Bcl2, Bax, mitROS, caspase-3 and RARP1; this leads to the induction of caspase-mediated intrinsic apoptosis, sub-G1 phase arrest and inhibition of cancer cell migration, which increase the anticancer effect on cervical cancer.