SS-a blocks the PI3K–Akt–mTOR cascade, elevates Bax and lowers Bcl-2, leading to S-phase arrest and apoptosis. It simultaneously provokes ER stress (GRP78–PERK–eIF2α–ATF4–CHOP), activates caspase-3/8/9 and enhances radiosensitivity in resistant GC cells. Here, EIF2AK3 is linked to gastric cancer.