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中华介入放射学电子杂志 ›› 2024, Vol. 12 ›› Issue (02) : 120 -125. doi: 10.3877/cma.j.issn.2095-5782.2024.02.004

基础研究

白花丹素抑制非小细胞肺癌细胞增殖的研究
梁美斯1, 兰慧敏2, 于婷2, 李胜桥3,()   
  1. 1. 519000 广东珠海,中山大学第五附属医院肿瘤中心中医肿瘤科;广东省分子成像工程技术研究中心
    2. 广东省分子成像工程技术研究中心
    3. 519000 广东珠海,中山大学第五附属医院肿瘤中心中医肿瘤科
  • 收稿日期:2024-02-24 出版日期:2024-05-25
  • 通信作者: 李胜桥
  • 基金资助:
    广东省中医药管理局课题(20211079); 珠海市科技创新局课题(2220004000322)

The study of plumbagin on suppressing the proliferation of non-small cell lung cancer

Meisi Liang1, Huimin Lan2, Ting Yu2, Shengqiao Li3,()   

  1. 1. Department of Chinese Medicine Oncology, Cancer Center, the Fifth Affiliated Hospital of Sun Yat-sen University, Guangdong Zhuhai 519000, China; Guangdong Provincial Engineering Research Center of Molecular Imaging, the Fifth Affiliated Hospital of Sun Yat-sen University, Guangdong Zhuhai 519000, China
    2. Guangdong Provincial Engineering Research Center of Molecular Imaging, the Fifth Affiliated Hospital of Sun Yat-sen University, Guangdong Zhuhai 519000, China
    3. Department of Chinese Medicine Oncology, Cancer Center, the Fifth Affiliated Hospital of Sun Yat-sen University, Guangdong Zhuhai 519000, China
  • Received:2024-02-24 Published:2024-05-25
  • Corresponding author: Shengqiao Li
引用本文:

梁美斯, 兰慧敏, 于婷, 李胜桥. 白花丹素抑制非小细胞肺癌细胞增殖的研究[J]. 中华介入放射学电子杂志, 2024, 12(02): 120-125.

Meisi Liang, Huimin Lan, Ting Yu, Shengqiao Li. The study of plumbagin on suppressing the proliferation of non-small cell lung cancer[J]. Chinese Journal of Interventional Radiology(Electronic Edition), 2024, 12(02): 120-125.

目的

探讨白花丹素抑制非小细胞肺癌(non-small cell lung cancer,NSCLC)的临床疗效。

方法

通过CCK-8实验检测白花丹素对LLC1细胞增殖的影响。同时构建Lewis肺癌模型,评估白花丹素对小鼠皮下肿瘤的治疗效果及其生物安全性。

结果

CCK-8实验结果表明,白花丹素可显著抑制LLC1细胞的增殖且呈现出时间依赖性和浓度依赖性。其作用机制与细胞凋亡和铁死亡相关。在Lewis肺癌模型中,与对照组相比,白花丹素治疗组具有更强的抗肿瘤作用。苏木精-伊红染色法结果显示,与对照组相比,白花丹素治疗后肿瘤组织内细胞核破裂增加,组织坏死面积扩大。

结论

细胞实验和动物实验均证实了白花丹素抑制NSCLC细胞的生长与增殖,且这种抑制作用与细胞凋亡和铁死亡相关。这为白花丹素治疗NSCLC提供了临床前依据。

Objective

To explore the tumour suppressing efficacy of plumbagin (PLB) on non-small cell lung cancer (NSCLC).

Methods

We used CCK-8 assay to detecte the effect of PLB on the proliferation of LLC1 cells and established a Lewis lung carcinoma model to evaluate the efficacy and biosafety of PLB in the treatment of subcutaneous tumor in mice.

Results

CCK-8 results showed that PLB significantly suppressed the proliferation of LLC1 cells in a time- and dose-dependent manner and its mechanisms were related to apoptosis and ferroptosis. In Lewis lung carcinoma model, PLB treatment group exhibited stronger antitumor effects versus the control group. The H&E results showed that, compared to the control group, there was an increase in cell nucleus rupture and tissue necrosis area with PLB treatment.

Conclusion

Both the results of cell and animal experiments confirmed that PLB suppressed the growth and proliferation of NSCLC cells, which may be related to cell apoptosis and ferroptosis. This provides a preclinical basis for treating NSCLC with PLB and promotes the development of new drugs.

图1 白花丹素对LLC1细胞增殖活性的影响(n = 3,±s不同浓度白花丹素与LLC1细胞共同孵育24、48和72 h后的细胞活性情况。
图2 细胞死亡抑制剂对白花丹素诱导的细胞死亡的影响(±sLLC1细胞用凋亡抑制剂Z-VAD(10 μmol/L)、铁死亡抑制剂去铁铵DFO(10 μmol/L)和铁抑素Fer-1(2.5 μmol/L)预处理3 h,再用白花丹素(3 μmol/L)处理24 h,然后进行CCK8检测。*P < 0.05,**P < 0.01。
图3 不同时间点小鼠肿瘤的体内生物发光成像(in vivo bioluminescence imaging,BLI)在指定时间通过活体生物发光成像监测小鼠体内肿瘤的生长情况。
图4 白花丹素体内抗肿瘤效果分析(±s4A:各组荷瘤小鼠治疗结束后的肿瘤图片;4B:各组荷瘤小鼠的平均肿瘤生长曲线;4C:各组荷瘤小鼠结束治疗后的肿瘤重量对比柱形图。*代表P < 0.05,**代表P < 0.01。
图5 荷瘤小鼠治疗后肿瘤组织H&E染色代表性图像比例尺:5A为2 000 μm;5B为50 μm。
图6 不同组别荷瘤小鼠的平均体质量变化曲线
图7 荷瘤小鼠治疗后各器官H&E染色代表性图像比例尺:7A、7C为2 000 μm;7B、7D为50 μm。
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