Hyaluronan inhibits postchemotherapy tumor regrowth in a colon carcinoma xenograft model.
Hyaluronan inhibits postchemotherapy tumor regrowth in a colon carcinoma xenograft model.
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DOI：
10.1158/1535-7163.mct-10-0529
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发表时间：
2010-11
影响因子：
5.7
通讯作者：
Khaldoyanidi SK
中科院分区：
文献类型：
--
作者：
Mueller BM;Schraufstatter IU;Goncharova V;Povaliy T;DiScipio R;Khaldoyanidi SK
癌症化疗最不良的后遗症是骨髓发育不全和全血细胞减少。我们最近证明，透明质酸 (HA) 有助于接受化疗药物的无肿瘤动物的造血恢复。然而，在荷瘤动物接受化疗后，残留的肿瘤细胞可能会对全身注射 HA 产生反应。因此，在这项研究中，我们研究了HA对化疗后残留肿瘤细胞再生长的影响。我们使用 HCT-8 人结肠癌细胞系作为模型，该细胞表达 HA 受体 CD44，结合外源 HA，并且在人/小鼠异种移植模型中对包含伊立替康和 5-氟尿嘧啶的化疗方案敏感。将 HCT-8 细胞植入 NOD/SCID 小鼠中，然后进行伊立替康/5-氟尿嘧啶治疗。经过三轮化疗后，无论有或没有HA，残余肿瘤都可以重新生长。与对照组相比，HA 治疗组的肿瘤再生长动态较慢。到肿瘤植入后第 5 周，与对照组相比，重新生长的肿瘤大小差异具有统计学显着性，并且与 HA 处理的肿瘤中较低的增殖和较高的细胞凋亡相关。这一发现提供了证据，证明HA治疗不会刺激而是延迟残留癌细胞的生长，这是确定HA的使用是否可以增强当前化疗策略的重要参数。
Among the most undesirable sequelae of chemotherapy for the treatment of cancer are bone marrow hypoplasia and pancytopenia. We recently demonstrated that hyaluronan (HA) facilitates hematopoietic recovery in tumor-free animals receiving chemotherapeutic agents. However, following a chemotherapeutic regime in tumor-bearing animals, it is possible that residual tumor cells might respond to systemic injections of HA. Thus, in this study we investigated the effect of HA on re-growth of residual tumor cells following chemotherapy. As a model we used HCT-8 human colon carcinoma cell line, which expresses the HA receptor CD44, binds exogenous HA and is susceptible to a chemotherapy protocol containing irinotecan and 5-fluorouracil in a human/mouse xenograft model. HCT-8 cells were implanted in NOD/SCID mice followed by irinotecan/5-fluorouracil treatment. After three rounds of chemotherapy, residual tumors were allowed to re-grow in the presence or absence of HA. The dynamics of tumor re-growth in the group treated with HA was slower compared to the control group. By week 5 after tumor implantation, the difference in the size of re-grown tumors was statistically significant and correlated with lower proliferation and higher apoptosis in HA-treated tumors as compared to controls. This finding provides evidence that HA treatment does not stimulate but delays growth of residual cancer cells, which is an important parameter in establishing whether the use of HA can enhance current chemotherapeutic strategies.