Suramin augments the antitumor and antimetastatic activity of pentoxifylline in B16F10 melanoma
Suramin augments the antitumor and antimetastatic activity of pentoxifylline in B16F10 melanoma
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DOI：
10.1002/ijc.22843
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发表时间：
2007-10-01
影响因子：
6.4
通讯作者：
Gude, Rajiv P.
中科院分区：
文献类型：
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作者：
Dua, Pooja;Ingle, Arvind;Gude, Rajiv P.
肿瘤快速生长和转移是与恶性黑色素瘤的治疗相关的2个主要问题。因此，能够干预这些过程的药物具有临床重要性。已显示，甲基黄嘌呤衍生物戊茶碱（PTX）抑制B16 F10黑色素瘤肿瘤生长和转移。我们假设苏拉明与PTX联合使用时会增强其抗肿瘤作用，我们已经使用B16 F10小鼠黑色素瘤模型进行了研究。苏拉明在同时或序贯组合增强PTX对B16 F10细胞的细胞毒作用。PTX使细胞阻滞在G 0-G1期，苏拉明增强了这种作用。两种药物都抑制F10与层粘连蛋白、基质胶和IV型胶原的粘附，并且在组合中显示出增强的抑制。与单一药物相比，组合还显示出对细胞运动性（p = 0.002）和通过基质胶的侵袭（p = 0.005）的显著更高的抑制。苏拉明与PTX对MMP-9明胶酶分泌的影响具有协同作用。将植入皮内B16 F10肿瘤的DBA 2/J小鼠用作研究肿瘤生长的模型。用50 mg/kg PTX、10 mg/kg苏拉明及其组合肿瘤内治疗动物。同时给药可抑制肿瘤生长5- 6倍。序贯方案中肿瘤生长完全阻断，部分病例肿瘤消退。肺转移结节的数量和大小也通过联合治疗显著减少。总之，PTX和苏拉明的新组合在B16 F10黑色素瘤中具有协同抗肿瘤和抗转移活性，并且可能是治疗患有恶性黑色素瘤的患者的有希望的方法。
Rapid tumor growth and metastasis are 2 major problems associated with treatment of malignant melanoma. Therefore, drugs that can intervene these processes are of clinical importance. Pentoxifylline (PTX), a methyl xanthine derivative, has been shown to inhibit B16F10 melanoma tumor growth and metastasis. We hypothesized that suramin when combined with PTX enhances its antineoplastic effects, which we have examined using the B16F10 mouse melanoma model. Suramin in simultaneous or sequential combination potentiated the cytotoxic effects of PTX on B16F10 cells. PTX arrested cells in the G0-G1 phase and suramin augmented the effects. Both the drugs inhibited F10 adhesion to laminin, matrigel and collagen type IV and showed enhanced inhibition in combination The combination also demonstrated significantly higher inhibition in cell motility (p = 0.002) and invasion through matrigel (p = 0.005) as compared to the single agents. Suramin synergized with PTX in its effects on secretion of MMP-9 gelatinase. DBA2/J mice implanted with intradermal B16F10 tumor were used as a model to study tumor growth. Animals were intratumorally treated with 50 mg/kg of PTX, 10 mg/kg of suramin and their combinations. Simultaneous administration of the drugs inhibited tumor growth by 5- to 6-folds. Tumor growth was completely blocked in sequential regimen with regression in some cases. The number and size of metastatic nodules on lung was also reduced significantly by the combination treatment. In conclusion, the novel combination of PTX and suramin has synergistic antitumor and antimetastatic activity in B16F10 melanoma and may be a promising approach in treatment of patients suffering from malignant melanoma.