Sequence-dependent effects of hematoporphyrin derivatives (HPD) photodynamic therapy and cisplatin on lung adenocarcinoma cells

Nana Li; Shichao Cui; Aizhen Yang; Baohong Xiao; Yiwei Cao; Xiaohui Yang; Cunzhi Lin

doi:10.1016/j.pdpdt.2024.104102

Sequence-dependent effects of hematoporphyrin derivatives (HPD) photodynamic therapy and cisplatin on lung adenocarcinoma cells

Photodiagnosis Photodyn Ther. 2024 Apr 26:104102. doi: 10.1016/j.pdpdt.2024.104102. Online ahead of print.

Authors

Nana Li¹, Shichao Cui², Aizhen Yang³, Baohong Xiao⁴, Yiwei Cao⁵, Xiaohui Yang⁶, Cunzhi Lin⁷

Affiliations

¹ Department of Respiratory and Critical Care Medicine, The Affiliated Hospital of Qingdao University, Qingdao 266003, China.. Electronic address: lnn112426@163.com.
² Department of Respiratory and Critical Care Medicine, The Affiliated Hospital of Qingdao University, Qingdao 266003, China.. Electronic address: qdcuishichao@163.com.
³ Department of Respiratory and Critical Care Medicine, The Affiliated Hospital of Qingdao University, Qingdao 266003, China.. Electronic address: yangaizhen1985@126.com.
⁴ Department of Respiratory and Critical Care Medicine, The Affiliated Hospital of Qingdao University, Qingdao 266003, China.. Electronic address: xiao-1997@outlook.com.
⁵ Department of Respiratory and Critical Care Medicine, The Affiliated Hospital of Qingdao University, Qingdao 266003, China.. Electronic address: cyw13198@163.com.
⁶ Department of Respiratory and Critical Care Medicine, The Affiliated Hospital of Qingdao University, Qingdao 266003, China.. Electronic address: yangxiaohui@qdu.edu.cn.
⁷ Department of Respiratory and Critical Care Medicine, The Affiliated Hospital of Qingdao University, Qingdao 266003, China.. Electronic address: lindoc@126.com.

PMID: 38679153
DOI: 10.1016/j.pdpdt.2024.104102

Abstract

Background: Hematoporphyrin derivatives (HPD)-Photodynamic therapy (PDT) in combination with cisplatin (DDP) is an effective anticancer strategy. However, whether the order of combination affects efficacy has not been studied.

Methods: The human lung adenocarcinoma (LUAD) A549 cells were used as the study subjects. After A549 cells were treated with a single medication (PDT/DDP) or a sequential combination (PDT + DDP / DDP + PDT), the cell viability was assayed using the cell counting kit-8 method. Hoechst staining, Annexin-V/propidium iodide (PI) double staining, western blotting, and a real-time quantitative polymerase chain reaction (RT-qPCR) were performed to examine the mechanisms behind the combined effects.

Results: A synergistic impact between HPD-PDT and DDP was found. The cell viability in the PDT+DDP group was significantly lower than in the DDP+PDT group. A significant apoptotic profile and a high apoptotic rate were seen in the PDT + DDP group. The western blot showed that the expression levels of Bcl2-associated x(Bax) and cleaved-poly ADP-ribose polymerase (PARP) increased, and those of B-cell lymphoma-2 (Bcl-2) and Caspase-9 decreased in the PDT + DDP group. At the same time, the RT-qPCR revealed the upregulation of Bax and PARP mRNA and the downregulation of Bcl-2 and Caspase-9 mRNA.

Conclusion: The order of the combination therapy (PDT + DDP / DDP + PDT) was important. The HPD-PDT followed by DDP significantly inhibited LUAD cell viability, which may be related to the mitochondrial apoptotic pathway.

Keywords: Apoptosis; Cisplatin; Combined therapy; Hematoporphyrin derivatives; Photodynamic therapy.