芝麻素对人肺腺癌化疗敏感性、侵袭性及免疫逃逸机制的影响

Lung adenocarcinoma (LUAD) is a major cause of cancer‑related mortality worldwide. Sesamin is a lignan with potent anticancer properties and promising therapeutic potential. In the present study, it was aimed to investigate the specific mechanisms through which sesamin reduces cell invasiveness and cancer‑associated immunosuppression in LUAD cells.

The effects of sesamin on LUAD cell invasiveness were investigated using a wound healing assay and anoikis resistance assay. NK‑92 MI cells were used to analyze cancer‑associated immunosuppression upon sesamin treatment. The therapeutic effect of sesamin in LUAD was measured using a subcutaneous mouse model.

Our results indicated that sesamin inhibited the proliferation, survival and migration of LUAD cells (A549 and CL1‑5) in a dose‑dependent manner. Sesamin also enhanced the proapoptotic effects of chemotherapeutic agents such as docetaxel and paclitaxel through the activation of the caspase‑3/poly(ADP‑ribose) polymerase pathway.

In addition, sesamin reduced cancer cell migration and anoikis resistance by downregulating the expression of N‑cadherin and inhibiting the phosphoinositide 3‑kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway. It also induced the downregulation of programmed death ligand 1 through hsa‑microRNA‑34a‑5p, resulting in the increased cytotoxicity of natural killer cells. This sequence of events consequently interfered with the immune evasion mechanism of LUAD cells.

In conclusion, sesamin has a multifaceted effect on the migration, anoikis resistance and antitumor immunity of LUAD cells, indicating its potential as adjunctive therapy.