Remmelink M, Salmon I, Delville J P, Goldschmidt D, Capel P, Gebhart M, Pasteels J L, Kiss R, Darro F
Laboratory of Histology, Faculty of Medecine, Free University of Brussels, Belgium.
Anticancer Res. 1997 May-Jun;17(3C):2009-17.
The benefit of performing chemotherapy on soft tissue sarcomas remains controversial. The present study deals with the in vitro characterisation of the influence of 3 antitumoral agents on the growth of 8 sarcoma cell lines.
Cell growth was monitored by means of the MTT colorimetric assay, which was further validated by a direct cell counting method. The three drugs tested included doxorubicin (ADR), cisplatin (DDP) and dacarbazine (DTIC). ADR was tested at 10(-5) M, 10(-6) M and 10(-7) M; DDP at 10(-5) M, 10(-6) M and 10(-7) M; and DTIC at 10(-3) M, 10(-4) M and 10(-5) M. A combination of the three drugs was also tested in order to ascertain whether a synergistic effect on cell growth inhibition could be obtained. A potential antineoplastic agent-induced influence on cell growth was determined 3 days after the addition of the diverse drug(s) to the culture media. The cell concentration was specifically adapted to each cell line. The 8 cell lines included 3 leiomyosarcomas, 1 malignant mixed Müllerian tumour, 3 rhabdomyosarcomas and 1 fibrosarcoma.
The results show that of the three drugs tested, ADR was the most efficient in terms of the level of cell growth inhibition obtained and the number of cell lines whose growth was significantly inhibited. Of the three drugs, the least active was DDP. A significant synergistic effect was observed when the three drugs were added together to the culture medium. This synergistic effect was evident at the lowest doses tested for each drug. Whatever the histopathological type, the 8 cell lines exhibited a wide range of response to chemotherapy.
The present study shows that the inhibition induced by 10(-7) M ADR, 10(-7) M DDP and 10(-5) M DTIC on sarcoma cell line growth is significantly more efficient than if each agent is tested individually. The in vitro methodology used here fits in with clinical reality because it enables sarcoma cell heterogeneity to be taken into account.
对软组织肉瘤进行化疗的益处仍存在争议。本研究探讨了3种抗肿瘤药物对8种肉瘤细胞系生长影响的体外特征。
通过MTT比色法监测细胞生长，并通过直接细胞计数法进一步验证。所测试的三种药物包括阿霉素（ADR）、顺铂（DDP）和达卡巴嗪（DTIC）。ADR的测试浓度为10⁻⁵M、10⁻⁶M和10⁻⁷M；DDP为10⁻⁵M、10⁻⁶M和10⁻⁷M；DTIC为10⁻³M、10⁻⁴M和10⁻⁵M。还测试了三种药物的组合，以确定是否能获得对细胞生长抑制的协同效应。在向培养基中添加不同药物3天后，确定潜在的抗肿瘤药物对细胞生长的影响。细胞浓度根据每种细胞系进行了专门调整。8种细胞系包括3种平滑肌肉瘤、1种恶性混合苗勒管肿瘤、3种横纹肌肉瘤和1种纤维肉瘤。
结果表明，在所测试的三种药物中，就获得的细胞生长抑制水平和生长受到显著抑制的细胞系数量而言，ADR最为有效。三种药物中，活性最低的是DDP。当三种药物一起添加到培养基中时，观察到显著的协同效应。这种协同效应在每种药物测试的最低剂量下都很明显。无论组织病理学类型如何，8种细胞系对化疗表现出广泛的反应。
本研究表明，10⁻⁷M ADR、10⁻⁷M DDP和10⁻⁵M DTIC对肉瘤细胞系生长的抑制作用明显比单独测试每种药物时更有效。这里使用的体外方法符合临床实际情况，因为它能够考虑到肉瘤细胞的异质性。
