Salvianolic acid A (Sal A) suppresses malignant progression of glioma and enhances temozolomide (TMZ) sensitivity via repressing transgelin-2 (TAGLN2) mediated phosphatidylinositol-3-kinase (PI3K) / protein kinase B (Akt) pathway

Glioma originated from excessively proliferative and highly invaded glial cells is a common intracranial malignant tumor with poor prognosis. Resistance to temozolomide (TMZ) is a clinical challenge in glioma treatment due to the fact that chemoresistance remains a main obstacle in the improvement of drug efficacy. Salvianolic acid A (Sal A), originated from traditional Chinese herbal medicine Salvia miltiorrhiza, possesses anti-tumor effects and could facilitate the delivery of drugs to brain tumor tissues. In the present work, effects of Sal A on the viability, proliferation, migration, invasion and apoptosis of human glioma cell line U87 cells as well as influence of Sal A on TMZ resistance were measured, so as to identify the biological function of Sal A in the malignant behaviors and chemoresistance of glioma cells. Additionally, activation of TAGLN2/PI3K/Akt pathway in glioma cells was also detected to investigate whether Sal A could regulate TAGLN2/PI3K/Akt to manipulate the progression of glioma and TMZ resistance. Results discovered that Sal A treatment reduced the viability, repressed the proliferation, migration and invasion of glioma cells as well as promoted the apoptosis of glioma cells. Besides, Sal A treatment suppressed TAGLN2/PI3K/Akt pathway in glioma cells. Sal A treatment strengthened the suppressing effect of TMZ on glioma cell proliferation and reinforced the promoting effect of TMZ on glioma cell apoptosis, which were abolished by upregulation of TAGLN2. To conclude, Sal A treatment could suppress the malignant behaviors of glioma cells and improve TMZ sensitivity through inactivating TAGLN2/PI3K/Akt pathway.

胶质瘤（Glioma）是一类起源于过度增殖且高侵袭性胶质细胞的常见颅内恶性肿瘤，预后较差。替莫唑胺（temozolomide, TMZ）耐药是胶质瘤临床治疗中的一大难题，化疗耐药始终是提升药物疗效的主要阻碍。丹酚酸A（Salvianolic acid A, Sal A）源自中药丹参（Salvia miltiorrhiza），兼具抗肿瘤活性与促进药物向脑肿瘤组织递送的能力。本研究检测了丹酚酸A对人胶质瘤细胞系U87（human glioma cell line U87）细胞的活力、增殖、迁移、侵袭及凋亡的影响，及其对TMZ耐药性的作用，以明确丹酚酸A在胶质瘤细胞恶性行为与化疗耐药中的生物学功能。此外，本研究还检测了胶质瘤细胞中TAGLN2/PI3K/Akt通路的激活状态，以探究丹酚酸A是否可通过调控TAGLN2/PI3K/Akt通路干预胶质瘤进展与TMZ耐药。研究结果表明，丹酚酸A处理可降低胶质瘤细胞活力，抑制其增殖、迁移与侵袭，并促进胶质瘤细胞凋亡。此外，丹酚酸A处理可抑制胶质瘤细胞内的TAGLN2/PI3K/Akt通路。丹酚酸A处理可增强替莫唑胺对胶质瘤细胞增殖的抑制作用，并强化替莫唑胺对胶质瘤细胞凋亡的促进作用，该作用可因TAGLN2的上调而被抵消。综上，丹酚酸A处理可通过失活TAGLN2/PI3K/Akt通路，抑制胶质瘤细胞的恶性行为并提升其对TMZ的敏感性。