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基于间四（羟苯基）二氢卟吩的光动力疗法联合顺铂对恶性Hep-2细胞的协同作用。

Synergistic effect of meta-tetra(hydroxyphenyl)chlorin-based photodynamic therapy followed by cisplatin on malignant Hep-2 cells.

作者信息

Xue Kai, Wang Yi-Nan, Zhao Xue, Zhang Hong-Xin, Yu Dan, Jin Chun-Shun

机构信息

Department of Otolaryngology-Head and Neck Surgery, The Second Hospital of Jilin University, Changchun 130041, People's Republic of China.

Department of Gynecology and Obstetrics, The Second Hospital of Jilin University, Changchun 130041, People's Republic of China.

出版信息

Onco Targets Ther. 2019 Jul 10;12:5525-5536. doi: 10.2147/OTT.S198422. eCollection 2019.

DOI:10.2147/OTT.S198422
PMID:31371990
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6636612/
Abstract

PURPOSE

Tumor drug resistance limits the response to chemotherapy. Interestingly, sequential combination therapy enhances the anticancer efficacy of drugs like cisplatin (CDDP) via synergistic effects. We assayed the synergistic effects of combined photodynamic therapy programmed death receptor-ligand 1 (PDT) and chemotherapy in malignant Hep-2 cells.

METHODS

In the cultured Hep-2 cells, meta-tetra(hydroxyphenyl)chlorin (m-THPC) and CDDP were administered separately or in combination. The cellular viability and apoptosis were assessed, accompanied by measurement of the expression of Bax, Bcl-2, ATG-7, and LC3 (LC3-I and LC3-II). Additionally, nuclear chromatin changes, drug retention, and PD-L1 expression were further investigated following different treatments.

RESULTS

The sequential treatment significantly diminished cell viability and induced cell apoptosis, in consistency with the usage of single therapeutic strategies, as reflected by an increase in Bax expression and decrease of Bcl-2 expression. Moreover, ATG-7 and LC3-II/LC3-I ratio were reduced after administration of the sequential treatment. Synergetic effect of nuclear chromatin configuration, negative effects of cellular drug retention, and a decrease in PD-L1 expression were observed following the sequential treatment.

CONCLUSION

The application of sequential treatment of PDT in combination with chemotherapy offers a promising therapeutic option for cancer treatment, by regulating the PD-L1 expression, autophagy, and non-mitochondrial pathways.

摘要

目的

肿瘤耐药性限制了化疗的疗效。有趣的是，序贯联合疗法通过协同作用增强了顺铂（CDDP）等药物的抗癌效果。我们检测了光动力疗法程序性死亡受体配体1（PDT）与化疗联合应用于恶性Hep-2细胞中的协同效应。

方法

在培养的Hep-2细胞中，分别单独或联合给予间-四（羟苯基）氯卟啉（m-THPC）和CDDP。评估细胞活力和凋亡情况，并测定Bax、Bcl-2、ATG-7和LC3（LC3-I和LC3-II）的表达。此外，在不同处理后进一步研究核染色质变化、药物滞留和PD-L1表达。

结果

序贯治疗显著降低细胞活力并诱导细胞凋亡，这与单一治疗策略的作用一致，表现为Bax表达增加和Bcl-2表达降低。此外，序贯治疗后ATG-7和LC3-II/LC3-I比值降低。序贯治疗后观察到核染色质构型的协同效应、细胞药物滞留的负面影响以及PD-L1表达的降低。

结论

序贯应用PDT联合化疗通过调节PD-L1表达、自噬和非线粒体途径，为癌症治疗提供了一种有前景的治疗选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2eae/6636612/de357b3d4745/OTT-12-5525-g0009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2eae/6636612/7f5bbfbd2585/OTT-12-5525-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2eae/6636612/17d987fcdb00/OTT-12-5525-g0002.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2eae/6636612/c1a7a658da0e/OTT-12-5525-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2eae/6636612/0ed02e4d2ce2/OTT-12-5525-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2eae/6636612/36388e820fda/OTT-12-5525-g0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2eae/6636612/a49832f917a5/OTT-12-5525-g0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2eae/6636612/de357b3d4745/OTT-12-5525-g0009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2eae/6636612/7f5bbfbd2585/OTT-12-5525-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2eae/6636612/17d987fcdb00/OTT-12-5525-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2eae/6636612/22f430d90e52/OTT-12-5525-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2eae/6636612/cb8ab6f31f8b/OTT-12-5525-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2eae/6636612/c1a7a658da0e/OTT-12-5525-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2eae/6636612/0ed02e4d2ce2/OTT-12-5525-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2eae/6636612/36388e820fda/OTT-12-5525-g0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2eae/6636612/a49832f917a5/OTT-12-5525-g0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2eae/6636612/de357b3d4745/OTT-12-5525-g0009.jpg

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