Department of Thoracic Surgery, The Second Hospital of Shandong University, Jinan, Shandong, China (mainland).
Department of Traumatic Orthopaedic Brotherhood of Surgical, The Second Hospital of Shandong University, Jinan, Shandong, China (mainland).
Med Sci Monit. 2020 Apr 11;26:e922092. doi: 10.12659/MSM.922092.
BACKGROUND Despite scientific advancement in radiotherapy and chemotherapy, the 5-year survival rate of lung cancer patients is around 15%. The present study explored the anticancer potential of betulinic acid nanoparticles against lung cancer cells. MATERIAL AND METHODS The proliferative changes in lung cancer cells by betulinic acid nanoparticles were measured by MTT assay. Cell cycle analysis was performed by flow cytometry using propidium iodide stain. Transwell and wound healing assay were used for determination of HKULC2 cell metastatic potential. RESULTS The betulinic acid nanoparticle treatment significantly (P<0.05) reduced proliferation of HKULC2, H1299, and H23 cells. The proliferation of HKULC2, H1299, and H23 cells was reduced to 33%, 28% and 24%, respectively on treatment with 10 µM of betulinic acid nanoparticles. The results from flow cytometry showed that betulinic acid nanoparticle exposure lead to cell cycle arrest in G1 phase in HKULC2 cells. Treatment with betulinic acid nanoparticles markedly decreased migration potential of HKULC2 cells. The invasive ability of HKULC2 cells was also suppressed markedly on exposure to betulinic acid nanoparticles. Western blotting of HKULC2 cells showed that betulinic acid nanoparticles promoted the expression of p21 and p53 and downregulated CD133, ALDH, BCL2, MCL1, and c-Myc expression. Betulinic acid nanoparticles reduced the expression of ABCG1 protein markedly. CONCLUSIONS The present study demonstrated that betulinic acid nanoparticles inhibit proliferation, metastatic ability, and arrest cell cycle in lung cancer cells through downregulation of ABCG1 oncogene expression. Therefore, betulinic acid nanoparticles may be used as therapeutic agent for the treatment of lung cancer.
尽管放疗和化疗方面取得了科学进步，但肺癌患者的 5 年生存率仍约为 15%。本研究探讨了白桦脂酸纳米粒对肺癌细胞的抗癌潜力。
用 MTT 法测定白桦脂酸纳米粒对肺癌细胞增殖的变化。用碘化丙啶染色通过流式细胞术进行细胞周期分析。Transwell 和划痕愈合试验用于测定 HKULC2 细胞的转移潜能。
白桦脂酸纳米粒治疗显著（P<0.05）降低了 HKULC2、H1299 和 H23 细胞的增殖。HKULC2、H1299 和 H23 细胞在 10 μM 白桦脂酸纳米粒处理下增殖分别减少到 33%、28%和 24%。流式细胞术结果表明，白桦脂酸纳米粒暴露导致 HKULC2 细胞周期停滞在 G1 期。白桦脂酸纳米粒处理明显降低了 HKULC2 细胞的迁移潜能。HKULC2 细胞的侵袭能力也在暴露于白桦脂酸纳米粒后明显受到抑制。HKULC2 细胞的 Western blot 显示，白桦脂酸纳米粒促进 p21 和 p53 的表达，并下调 CD133、ALDH、BCL2、MCL1 和 c-Myc 的表达。白桦脂酸纳米粒明显降低了 ABCG1 蛋白的表达。
本研究表明，白桦脂酸纳米粒通过下调 ABCG1 癌基因表达，抑制肺癌细胞的增殖、转移能力和细胞周期停滞。因此，白桦脂酸纳米粒可作为治疗肺癌的治疗剂。
