背景:犬乳腺肿瘤(CMGT)是异质性肿瘤,与人类乳腺癌具有许多相似的特征。尽管目前的治疗方案有所改善,在CMGTs的治疗中,需要新的治疗方式来有效地杀死肿瘤细胞而没有一般毒性。光动力疗法(PDT)是一种有前途的癌症治疗方法。然而,有一项有限的研究评估了PDT治疗CMGT的疗效.
方法:在这种情况下,我们,第一次,通过不同的分子分析研究了5-氨基酮戊酸(5-ALA)介导的PDT在6和12J/cm2下在两种不同亚型[肾小管乳头状癌(TPC)和癌肉瘤(CS)]细胞中的治疗潜力。通过细胞内PpIX水平分析5-ALA/PDT对这些细胞的细胞毒性作用,WST-1和ROS分析。此外,5-ALA/PDT介导的细胞凋亡效应对TPC和CS细胞的潜在分子机制进行了评估膜联蛋白V,AO/PI,RT-PCR和蛋白质印迹分析。
结果:照射后的5-ALA/PDT处理大大抑制了TPC和CS细胞的活力(p<0.01),并通过升高的ROS水平引起凋亡死亡,Caspase-9和Caspase-3的激活以及Bax的过表达。然而,TPC和CS细胞对5-ALA/PDT的反应不同。
结论:我们的初步体外研究结果为TPC和CS细胞中5-ALA/PDT介导的凋亡的分子机制提供了新的见解。然而,CMGT细胞对5-ALA/PDT的治疗反应有限。
BACKGROUND: Canine mammary gland tumors (CMGTs) are heterogeneous tumors and share many similar features with human breast cancer. Despite the improvement of current treatment options, new treatment modalities are required to effectively kill tumor cells without general toxicity in the treatment of CMGTs. Photodynamic therapy (PDT) is a promising method for cancer treatment. However, there is a limited
study evaluating the therapeutic efficacy of PDT in the treatment of CMGTs.
METHODS: In this context, we, for the first time, investigated the therapeutic potential of 5-aminolaevulinic acid (5-ALA) mediated PDT at 6 and 12 J/cm2 in two different subtypes [Tubulopapillary carcinoma (TPC) and carcinosarcoma (CS)] cells via different molecular analysis. The cytotoxic effects of 5-ALA/PDT on these cells were analyzed by intracellular PpIX level, WST-1 and ROS analysis. Furthermore, the underlying moleculer mechanism of 5-ALA/PDT mediated apoptotic effects on TPC and CS cells were evaluated Annexin V, AO/PI, RT-PCR and western blot analysis.
RESULTS: The 5-ALA/PDT treatment upon irradiation considerably inhibited the viability of both TPC and CS cells (p<0.01) and caused apoptotic death through elevated ROS levels, the activation of Caspase-9, and Caspase-3, and the overexpression of Bax. However, the response of TPC and CS cells to 5-ALA/PDT was different.
CONCLUSIONS: Our preliminary in vitro findings provide novel insights into the molecular mechanisms underlying 5-ALA/PDT mediated apoptosis in both TPC and CS cells. However, the therapeutic response of CMGT cells to 5-ALA/PDT is limited.