2,3'-ジヒドロキシ-5'-メトキシスチルベンのAKT依存性メカニズムを介した非小細胞肺癌細胞株に対する抗がん活性：包括的なinvitroおよび計算解析

Lung cancer remains a major clinical challenge, with therapy resistance in non-small-cell lung cancer (NSCLC) driving the search for novel selective agents. This study demonstrates that 2,3'-dihydroxy-5'-methoxystilbene exhibits significant anticancer activity in NSCLC cell lines (A549, H23, and H460) while displaying substantially lower toxicity toward normal NIH/3T3 fibroblasts. The compound reduced the viability of H23 and H460 cells after 48 h. (IC50: 23.39 ± 3.27 μM and 24.20 ± 2.61 μM, respectively), with NIH/3T3 cells remaining comparatively resistant (IC50 > 100 μM). At 25 μM, it suppressed proliferation by approximately 40% in H23, 30% in H460, and 20% in A549 cells, and dose-dependently impaired colony formation and migration, leading to near-complete migration arrest in H460 cells. Apoptosis induction peaked at 19% in H23, 17% in H460, and 8% in A549 cells at 25 μM. Mechanistic studies and molecular modeling revealed AKT-dependent activity, with decreased p-AKT and p-GSK3β levels (0.70 and 0.75 in H23; 0.65 and 0.70 in H460 at 25 μM), without changes in total protein expression. Combination treatment with cisplatin yielded synergistic effects in A549 (CI = 0.83) and H460 (CI = 0.94) cells, but antagonistic effects in H23 cells (CI = 1.32). These findings identify 2,3'-dihydroxy-5'-methoxystilbene as a selective AKT-targeting stilbene with promising anticancer potential and context-dependent chemosensitizing activity in NSCLC cells.