Liang Minjie, Wu Yayun, Sun Jimin, Zhao Ya, Liu Lijuan, Zhao Ruizhi, Wang Yan
School of Chinese Materia Medica, Guangdong Pharmaceutical University, Guangzhou 510006, China.
State Key Laboratory of Dampaness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510006, China.
ACS Omega. 2024 Apr 14;9(16):18375-18384. doi: 10.1021/acsomega.4c00364. eCollection 2024 Apr 23.
Oxaliplatin (OXA) is recognized as a first-line drug for gastric cancer. However, low accumulation of the OXA in the target site and the development of drug resistance directly led to treatment failure. In the present study, an ultrasonic extraction method for (DC.) Koidz. polysaccharides (AKUs) and the combination treatment with OXA in vitro were studied. Results showed that when the pH level was 11, the ultrasound power at 450 W, the solid-liquid ratio was 1:20, and the ultrasound treatment for 30 min, the yield of AKUs was significantly increased to 13.20 ± 0.35%. The molecular weights of the AKUs ranged from 7.21 to 185.94 kDa, and its monosaccharides were mainly composed of arabinose (Ara), galactose (Gal), and glucose (Glu) with a ratio of 58.36, 16.90, and 15.49%, respectively. Cell experiments showed that, compared to OXA alone (2 μg/mL, inhibition rate of 18%), the treatment of OXA with AKUs had a significant synergistic inhibitory effect on MKN45 proliferation, which increased to 33, 41, and 45% with increasing AKUs concentrations (5-50 μg/mL), respectively, representing a 2.5-fold inhibition. Inductively coupled plasma-mass spectrometry (ICP-MS) determination confirmed that AKUs significantly increased the intracellular uptake of OXA by 29%, compared to that of OXA alone. We first demonstrated that the combined synergistic inhibitory effect of AKUs and OXA on gastric cancer cells was mediated by reducing the expression of efflux proteins (MRP1 and MRP2) and increasing the expression of ingested protein (OCT2). As a result of the above, AKUs deserved to be an effective adjuvant combined with chemotherapeutics in a clinical setting.
奥沙利铂（OXA）被公认为是治疗胃癌的一线药物。然而，OXA在靶部位的低蓄积以及耐药性的产生直接导致治疗失败。在本研究中，研究了对（DC.）Koidz.多糖（AKUs）的超声提取方法以及OXA与AKUs的体外联合治疗。结果表明，当pH值为11、超声功率为450W、固液比为1:20且超声处理30分钟时，AKUs的产率显著提高至13.20±0.35%。AKUs的分子量范围为7.21至185.94 kDa，其单糖主要由阿拉伯糖（Ara）、半乳糖（Gal）和葡萄糖（Glu）组成，比例分别为58.36%、16.90%和15.49%。细胞实验表明，与单独使用OXA（2μg/mL，抑制率为18%）相比，OXA与AKUs联合处理对MKN45增殖具有显著的协同抑制作用，随着AKUs浓度（5 - 50μg/mL）的增加，抑制率分别提高到33%、41%和45%，抑制作用增强了2.5倍。电感耦合等离子体质谱（ICP - MS）测定证实，与单独使用OXA相比，AKUs显著提高了OXA的细胞内摄取量29%。我们首次证明，AKUs和OXA对胃癌细胞的联合协同抑制作用是通过降低外排蛋白（MRP1和MRP2）的表达以及增加摄取蛋白（OCT2）的表达来介导的。基于上述结果，AKUs值得作为一种有效的佐剂在临床环境中与化疗药物联合使用。
