Sha Jun, Cao Dandan, Cui Rui, Xia Lu, Hua Xin, Lu Yuan, Han Shuhua
Department of Respiratory Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing City, Jiangsu Province, People's Republic of China.
Medicine Department of Southeast University, Nanjing, Jiangsu, People's Republic of China.
Cancer Manag Res. 2020 Nov 3;12:11077-11083. doi: 10.2147/CMAR.S278673. eCollection 2020.
Mannose, a major monosaccharide component of N-glycans, involves in the glycometabolism of human body. Recently, mannose has been shown to suppress tumor growth through enhancing chemosensitivity and reducing the activity of mannose phosphate isomerase (MPI). However, it is largely unknown whether mannose exerts effects on non-small cell lung cancer (NSCLC).
First, a mannose IC50 assay was conducted to find a suitable concentration of mannose for cell experiments. Then, vitro studies including CCK-8 assay, scratch wound healing assay, and TUNEL assay were performed to evaluate the effects of mannose on A549 cells, and an animal model was established to evaluate the antitumoural effect of mannose on NSCLC in vivo. Finally, immunohistochemistry was done to detect the expression of MPI by Rabbit Anti-MPI.
In this study, a concentration of mannose, 15mM, was used to explore the suppressive effect of mannose on A549 cells. CCK-8 assay demonstrated that mannose significantly inhibited the proliferation of A549 cells and enhanced the anti-tumor efficacy of carboplatin. Wound healing assay showed that mannose inhibits the migration of A549 cells, and mannose-induced migration inhibition was more efficient in A549 cells treated with carboplatin. TUNEL assay demonstrated that mannose significantly enhanced the efficacy of carboplatin to promote apoptosis treated by mannose (15mM) or carboplatin. The results of animal experiments revealed that the size and weight of tumors derived from A549 cells treated with mannose were smaller than those derived from control cells, and co-treatment with mannose and carboplatin had most efficient inhibition on tumor growth. MPI expression detection showed that the expression level of MPI in the stage Tis (tumor in situ) was the highest, while the stage IV has the lowest.
Collectively, our findings suggest that mannose inhibited cell proliferation and migration, promoted cell apoptosis and enhanced the efficacy of carboplatin in lung adenocarcinoma. Preliminary results showed that mannose had less side effect on health. In the future, mannose may be a potential candidate drug for adjuvant therapy of lung adenocarcinoma.
甘露糖是N-聚糖的主要单糖成分，参与人体糖代谢。最近，研究表明甘露糖可通过增强化疗敏感性和降低磷酸甘露糖异构酶（MPI）的活性来抑制肿瘤生长。然而，甘露糖对非小细胞肺癌（NSCLC）是否有作用在很大程度上尚不清楚。
首先，进行甘露糖IC50测定以确定适合细胞实验的甘露糖浓度。然后，进行包括CCK-8测定、划痕伤口愈合测定和TUNEL测定在内的体外研究，以评估甘露糖对A549细胞的影响，并建立动物模型以评估甘露糖在体内对NSCLC的抗肿瘤作用。最后，通过兔抗MPI进行免疫组织化学检测MPI的表达。
在本研究中，使用15mM浓度的甘露糖来探究其对A549细胞的抑制作用。CCK-8测定表明，甘露糖显著抑制A549细胞的增殖，并增强卡铂的抗肿瘤疗效。伤口愈合测定表明，甘露糖抑制A549细胞的迁移，并且在卡铂处理的A549细胞中，甘露糖诱导的迁移抑制更有效。TUNEL测定表明，甘露糖显著增强了卡铂促进凋亡的疗效，无论是经甘露糖（15mM）还是卡铂处理。动物实验结果显示，用甘露糖处理的A549细胞产生的肿瘤大小和重量均小于对照细胞产生的肿瘤，甘露糖与卡铂联合处理对肿瘤生长的抑制作用最为有效。MPI表达检测表明，MPI在Tis期（原位肿瘤）的表达水平最高，而在IV期最低。
总体而言，我们的研究结果表明，甘露糖可抑制肺腺癌细胞的增殖和迁移，促进细胞凋亡，并增强卡铂的疗效。初步结果表明，甘露糖对健康的副作用较小。未来，甘露糖可能是肺腺癌辅助治疗的潜在候选药物。
