IR-780 enhances cytotoxicity of adriamycin against cancer stem-like cells from hepatocellular carcinoma cells

Xingyun Liao; Yang Wang; Jianguo Sun; Xin Wang; Chunmeng Shi

doi:10.16016/j.1000-5404.201611066

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IR-780 enhances cytotoxicity of adriamycin against cancer stem-like cells from hepatocellular carcinoma cells

Basic Medicine | 更新时间：2026-01-09

- IR-780 enhances cytotoxicity of adriamycin against cancer stem-like cells from hepatocellular carcinoma cells
- Journal of Third Military Medical University Vol. 39, Issue 12, Pages: 1206-1212(2017)
- 作者机构：
  
  1.400038 重庆，第三军医大学军事预防医学院全军复合伤研究所，创伤、烧伤与复合伤国家重点实验室
  2.400037 重庆，第三军医大学新桥医院全军肿瘤研究所
- 作者简介：
- 基金信息：
  
  the Key Program of National Natural Science Foundation of China(81130026);the Innovative Program of Graduate Student of Chongqing(2014)
- DOI：10.16016/j.1000-5404.201611066
  CLC： R73-36;R735.7;R979.14
- Received：08 November 2016，
  
  Revised：2017-02-10，
  
  Published：30 June 2017
- 稿件说明：
移动端阅览
Xingyun Liao, Yang Wang, Jianguo Sun, et al. IR-780 enhances cytotoxicity of adriamycin against cancer stem-like cells from hepatocellular carcinoma cells[J]. Journal of Third Military Medical University, 2017, 39(12): 1206-1212.
DOI：

Xingyun Liao, Yang Wang, Jianguo Sun, et al. IR-780 enhances cytotoxicity of adriamycin against cancer stem-like cells from hepatocellular carcinoma cells[J]. Journal of Third Military Medical University, 2017, 39(12): 1206-1212. DOI： 10.16016/j.1000-5404.201611066.

摘要

目的

探讨七甲川花菁类荧光小分子IR-780联合阿霉素对肝癌干细胞样细胞的杀伤作用。

方法

利用CCK-8试剂盒检测不同浓度IR-780(0、1.250、2.500、5.000、10.000、20.000 μmol/L)及IR-780联合阿霉素(0、0.025、0.050、0.100、0.200、0.400 μmol/L)对4种不同肝癌细胞(QGY-7703、SMMC-7721、Huh-7和HepG2) 的杀伤效应，并确定后续实验IR-780和阿霉素的浓度，采用细胞划痕实验检测IR-780联合阿霉素对肝癌细胞迁移能力的影响；采用无血清悬浮培养的方法从Huh-7细胞株中分离并鉴定出具有干细胞特性的肿瘤细胞，检测IR-780联合阿霉素对肝癌干细胞样细胞的杀伤作用及迁移能力的影响；在裸鼠皮下荷瘤模型中观察IR-780联合阿霉素对肝癌干细胞样细胞生长的抑制作用。

结果

低浓度的IR-780对肝癌细胞无明显杀伤作用；采用1.250 μmol/L的IR-780联合阿霉素可对多种肝癌细胞产生较强的杀伤作用，其中半数致死浓度LC

较单药阿霉素降低25%；采用无血清悬浮培养的方法培养出Huh-7细胞肿瘤球，比较其与贴壁细胞的克隆形成能力、致瘤能力和细胞周期分布，证明悬浮培养的肿瘤细胞具有肿瘤干细胞特性；IR-780联合阿霉素对肝癌干细胞样细胞具有较强的杀伤作用，单用阿霉素和IR-780联合阿霉素对肝癌干细胞样细胞的LC

差异有统计学意义[(0.30±0.02)

(0.22±0.04)μ

mol/L，

0.05

]

；IR-780联合阿霉素可明显抑制肝癌干细胞样细胞的迁移能力和裸鼠皮下肿瘤的生长。

结论

IR-780可增强阿霉素的抗肿瘤作用，提高对肝癌干细胞样细胞的杀伤效应。

Abstract

Objective

To determine the cytotoxic effects of adriamycin (ADM) in combination with heptamethine cyanine dye IR-780 iodide on cancer stem-like cells from hepatocellular carcinoma (HCC) cell line.

Methods

CCK-8 assay was used to detect the cell viability and LC

of ADM in the HCC cell lines QGY-7703

SMMC-7721

Huh-7 and HepG2 treated with IR-780 (0

1.250

2.500

5.000

10.000 or 20.000 μmol/L) alone or in combination with ADM (0

0.025

0.050

0.100

0.200 and 0.400 μmol/L). The effect of IR-780 combined with ADM on cell migration was assessed with scratch wound healing assay. Cancer stem-like cells were isolated from Huh-7 cells cultured in serum-free medium under non-adherent conditions and identified for their stemness. The effects of IR-780 combined with ADM on the cell viability

migration

and tumorigenicity of the cancer stem-like cells were evaluated both

in vitro

and inanude mouse model bearing the cell xenograft.

Results

Low-dose IR-780 (1.250 μmol/L) produced no significant cytotoxicity in the HCC cell lines. IR-780 at 1.250 μmol/L combined with ADM resulted inastrong cytotoxic effect in the cell lines withareduced LC

of ADM by 25% compared to that of ADM used alone. Comparison of the colony formation and tumorigenic abilities and cell cycle distribution between Huh-7 tumorspheres cultured in serum-free medium and the adherent cells demonstrated the stemness of the isolated cells. IR-780 combined with ADM showedastronger cytotoxic effect than ADM alone in the cancer stem-like cells withasignificantly reduced LC

of ADM (0.22±0.04

0.30±0.02 μmol/L

0.05). The combination of IR-780 and ADM

significantly inhibited the migration and tumorigenicity of the cancer stem-like cells both

in vitro

and in the tumor-bearing nude mouse model.

Conclusion

IR-780 can enhances the cytotoxic effect of ADM against cancer stem-like cells isolated from HCC cells.

关键词

Keywords

references

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