Zhang Lei, Wu Chengyu, Bouvet Michael, Yano Shuya, Hoffman Robert M
AntiCancer, Inc., San Diego, CA, USA.
Department of Traditional Chinese Medicine Diagnostics, Nanjing University of Traditional Chinese Medicine, Nanjing, China.
Oncotarget. 2015 Mar 10;6(7):5292-8. doi: 10.18632/oncotarget.2983.
We used the fluorescence ubiquitination-based cell cycle indicator (FUCCI) to monitor cell cycle arrest after treatment of FUCCI-expressing HeLa cells (FUCCI-HeLa) with a traditional Chinese medicine (TCM) herbal mixture LQ, previously shown to have anti-tumor and anti-metastatic activity in mouse models. Paclitaxel was used as the positive control. In 2D monolayer culture, the untreated control had approximately 45% of the cells in S/G₂/M phase. In contrast, the LQ-treated cells (9 mg/ml) were mostly in the G₀/G₁ (>90%) after 72 hours. After treatment with paclitaxel (0.01 μm), for 72 hours, 95% of the cells were in S/G₂/M. In 2.5D Matrigel culture, the colonies in the untreated control group had 40% of the cells in S/G₂/M. LQ arrested the cells in G₀/G₁ after 72 hours. Paclitaxel arrested almost all the cells in S/G₂/M after 72 hours. In 3D Gelfoam culture, the untreated control culture had approximately 45% of cells in G₂/M. In contrast, the LQ-treated cells were mostly in G₀/G₁ phase (>80%) after 72 hours treatment. Paclitaxel resulted in 90% of the cells arrested in S/G₂/M after 72 hours. The present report suggests the non-toxic LQ has potential to maintain cancers in a quiescent state for long periods of time.
我们使用基于荧光泛素化的细胞周期指示剂(FUCCI)来监测用中药复方LQ处理表达FUCCI的HeLa细胞(FUCCI-HeLa)后的细胞周期阻滞情况,先前已证明该复方在小鼠模型中具有抗肿瘤和抗转移活性。紫杉醇用作阳性对照。在二维单层培养中,未处理的对照组约45%的细胞处于S/G₂/M期。相比之下,用LQ(9 mg/ml)处理72小时后的细胞大多处于G₀/G₁期(>90%)。用紫杉醇(0.01μm)处理72小时后,95%的细胞处于S/G₂/M期。在2.5D基质胶培养中,未处理对照组的集落中有40%的细胞处于S/G₂/M期。LQ处理72小时后使细胞停滞在G₀/G₁期。紫杉醇处理72小时后几乎使所有细胞停滞在S/G₂/M期。在三维明胶海绵培养中,未处理的对照培养物中约45%的细胞处于G₂/M期。相比之下,用LQ处理72小时后的细胞大多处于G₀/G₁期(>80%)。紫杉醇处理72小时后导致90%的细胞停滞在S/G₂/M期。本报告表明无毒的LQ有潜力使癌症长期维持在静止状态。