Immunology Research Center, Tabriz University of Medical Sciences, Tabriz 51666-14731, Iran.
Student Research Committee, Tabriz University of Medical Sciences, Tabriz 51666-14731, Iran.
Molecules. 2021 Nov 15;26(22):6877. doi: 10.3390/molecules26226877.
Photodynamic therapy (PDT) is a light-based cancer therapy approach that has shown promising results in treating various malignancies. Growing evidence indicates that cancer stem cells (CSCs) are implicated in tumor recurrence, metastasis, and cancer therapy resistance in colorectal cancer (CRC); thus, targeting these cells can ameliorate the prognosis of affected patients. Based on our bioinformatics results, SOX2 overexpression is significantly associated with inferior disease-specific survival and worsened the progression-free interval of CRC patients. Our results demonstrate that zinc phthalocyanine (ZnPc)-PDT with 12 J/cm or 24 J/cm irradiation can substantially decrease tumor migration via downregulating MMP9 and ROCK1 and inhibit the clonogenicity of SW480 cells via downregulating CD44 and SOX2. Despite inhibiting clonogenicity, ZnPc-PDT with 12 J/cm irradiation fails to downregulate CD44 expression in SW480 cells. Our results indicate that ZnPc-PDT with 12 J/cm or 24 J/cm irradiation can substantially reduce the cell viability of SW480 cells and stimulate autophagy in the tumoral cells. Moreover, our results show that ZnPc-PDT with 12 J/cm or 24 J/cm irradiation can substantially arrest the cell cycle at the sub-G1 level, stimulate the intrinsic apoptosis pathway via upregulating caspase-3 and caspase-9 and downregulating Bcl-2. Indeed, our bioinformatics results show considerable interactions between the studied CSC-related genes with the studied migration- and apoptosis-related genes. Collectively, the current study highlights the potential role of ZnPc-PDT in inhibiting stemness and CRC development, which can ameliorate the prognosis of CRC patients.
光动力疗法（PDT）是一种基于光线的癌症治疗方法，已在治疗各种恶性肿瘤方面显示出良好的效果。越来越多的证据表明，癌症干细胞（CSC）与结直肠癌（CRC）中的肿瘤复发、转移和癌症治疗耐药性有关；因此，靶向这些细胞可以改善受影响患者的预后。根据我们的生物信息学结果，SOX2 的过表达与疾病特异性生存率降低显著相关，并恶化了 CRC 患者的无进展间隔。我们的结果表明，锌酞菁（ZnPc）-PDT 联合 12 J/cm 或 24 J/cm 的照射可以通过下调 MMP9 和 ROCK1 显著减少肿瘤迁移，并通过下调 CD44 和 SOX2 抑制 SW480 细胞的集落形成能力。尽管抑制了集落形成能力，但 ZnPc-PDT 联合 12 J/cm 的照射未能下调 SW480 细胞中的 CD44 表达。我们的结果表明，ZnPc-PDT 联合 12 J/cm 或 24 J/cm 的照射可以显著降低 SW480 细胞的细胞活力，并刺激肿瘤细胞中的自噬。此外，我们的结果表明，ZnPc-PDT 联合 12 J/cm 或 24 J/cm 的照射可以使细胞周期在 sub-G1 水平显著停滞，通过上调 caspase-3 和 caspase-9 并下调 Bcl-2 来刺激内在凋亡途径。事实上，我们的生物信息学结果显示，研究的 CSC 相关基因与研究的迁移和凋亡相关基因之间存在显著的相互作用。总的来说，本研究强调了 ZnPc-PDT 在抑制干性和 CRC 发展方面的潜力，这可以改善 CRC 患者的预后。
