Induction of Apoptosis of Human Cisplatin-resistance Lung Cancer Cells with MPPa-photodynamic Therapy_Journal of Biomedical Engineering

Authors：

1. Department of Obstetrics and Gynecology, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China;
2. Department of Rehabilitation Medicine, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China;

Corresponding author：

Keywords：

MPPa photodynamic therapy; cisplatin-resistance; reactive oxygen species; mitochondrial apoptosis

DOI：

10.7507/1001-5515.20160119

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Lung cancer is the leading cause of cancer-related deaths worldwide. Despite the development and use of several targeting drugs for lung cancer therapy, the five-year survival rate has remained as low as 15% for the past three decades. Cisplatin-based chemotherapy is considered the first-line therapeutic strategy for lung cancer. However, developments of chemoresistance is a major obstacle for the successful treatment. Therefore, the development of novel therapy against cisplatin-resistance lung cancer is imperative. Photodynamic therapy (PDT), which is a non-invasive combinatorial therapeutic modality using light, photosensitizer (PS) and oxygen, may provide an unprecedented tool to develop more effective treatments. To provide experimental basis for its application in cisplatin-resistance lung cancer, we will discuss the biological effects of MPPa-photodynamic therapy in human cisplatin-resistance lung cancer cells in this article. Human cisplatin-resistance lung cancer cells A549/DDP were co-cultured with MPPa (0, 1, 2, 4, 8, 16 μmol/L) and exposed to light (0, 0.6, 1.2, 2.4, 3.6, 4.8 J/cm²), and cell viability was determined with CCK-8 assay. Flow cytometry was used to detect apoptosis, DCFH-DA staining was employed to observe reactive oxygen species (ROS), and Western blot was used to detect the expressions of B-cell lymphoma-2 (Bcl-2) protein and Bcl-2 associated X protein (Bax). The proliferation of A549/DDP cells was suppressed by PDT. The apop-totic rate in the PDT group was significantly higher than that in the control, MPPa or light group (P < 0.05). The level of ROS was increased. The expression of Bax was increased, and that of Bcl-2 was decreased. MPPa-photodynamic therapy can significantly suppress cell viability, and induce apoptosis in human cisplatin-resistance lung cancer cells.

Citation： LUOLi, YUTinghe, BAIDingqun, HULina. Induction of Apoptosis of Human Cisplatin-resistance Lung Cancer Cells with MPPa-photodynamic Therapy. Journal of Biomedical Engineering, 2016, 33(4): 729-734. doi: 10.7507/1001-5515.20160119 Copy

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1. FERLAY J, SHIN H R, BRAY F, et al. Estimates of worldwide burden of cancer in 2008:GLOBOCAN 2008[J]. Int J Cancer, 2010, 127(12):2893-2917.
2. MALVEZZI M, BERTUCCIO P, LEVI F, et al. European cancer mortality predictions for the year 2014[J]. Ann Oncol, 2014, 25(8):1650-1656.
3. IMIELINSKI M, BERGER A H, HAMMERMAN P S, et al. Mapping the hallmarks of lung adenocarcinoma with massively parallel sequencing[J]. Cell, 2012, 150(6):1107-1120.
4. TISEO M, ARDIZZONI A, BONI Luca. First-line chemotherapy treatment of advanced non-small-cell lung cancer:does cisplatin versus carboplatin make a difference?[J]. J Thorac Oncol, 2014, 9(11):e82.
5. SANTANA-DAVILA R, SZABO A, ARCE-LARA C, et al. Cisplatin versus carboplatin-based regimens for the treatment of patients with metastatic lung cancer. An analysis of Veterans Health Administration data[J]. J Thorac Oncol, 2014, 9(5):702-709.
6. NELKE K H, PAWLAK W, LESZCZYSZYN J, et al. Photodynamic therapy in head and neck Cancer[J]. Postepy Hig Med Dosw (Online), 2014, 68:119-128.
7. SONG Jiaxing, CHEN Qun, XING Da. Enhanced apoptotic effects by downregulating Mcl-1:evidence for the improvement of photodynamic therapy with Celecoxib[J]. Exp Cell Res, 2013, 319(10):1491-1504.
8. LUO Ting, WILSON B C, LU Qingbin. Evaluation of one-and two-photon activated photodynamic therapy with pyropheophorbide-a methyl ester in human cervical, lung and ovarian Cancer cells[J]. J Photochem Photobiol B, 2014, 132:102-110.
9. GALLUZZI L, SENOVILLA L, VITALE I, et al. Molecular mechanisms of cisplatin resistance[J]. Oncogene, 2012, 31(15):1869-1883.
10. AGOSTINIS P, BERG K, CENGEL K A, et al. Photodynamic therapy of cancer:an update[J]. CA Cancer J Clin, 2011, 61(4):250-281.
11. STYLLI S S, KAYE A H. Photodynamic therapy of cerebral glioma——a review Part Ⅰ——a biological basis[J]. J Clin Neurosci, 2006, 13(6):615-625.
12. YOON I, LI Jiazhu, SHIM Y K. Advance in photosensitizers and light delivery for photodynamic therapy[J]. Clin Endosc, 2013, 46(1):7-23.
13. ALMEIDA R D, MANADAS B J, CARVALHO A P, et al. Intracellular signaling mechanisms in photodynamic therapy[J]. Biochimica et Biophysica Acta-Reviews on Cancer, 2004, 1704(2):59-86.
14. BITTREMIEUX M, BULTYNCK G. p53 and Ca²⁺ signaling from the endoplasmic reticulum:Partners in anti-cancer therapies[J]. Oncoscience, 2015, 2(3):233-238.
15. WU C C, BRATTON S B. Regulation of the intrinsic apoptosis pathway by reactive oxygen species[J]. Antioxid Redox Signal, 2013, 19(6):546-558.
16. D'ALESSIO M, DE NICOLA M, COPPOLA S, et al. Oxidative Bax dimerization promotes its translocation to mitochondria independently of apoptosis[J]. FASEB J, 2005, 19(11):1504-1506.
17. OGILBY P R. Singlet oxygen:there is indeed something new under the sun[J]. Chem Soc Rev, 2010, 39(8):3181-3209.
18. OLEINICK N L, MORRIS R L, BELICHENKO I. The role of apoptosis in response to photodynamic therapy:what, where, why, and how[J]. Photochem Photobiol Sci, 2002, 1(1):1-21.
19. LIHUAN Du, JINGCUN Zheng, NING Jiang, et al. Photodynamic therapy with the novel photosensitizer chlorophyllin f induces apoptosis and autophagy in human bladder cancer cells[J]. Lasers Surg Med, 2014, 46(4):319-334.
20. MROZ P, YAROSLAVSKY A, KHARKWAL G B, et al. Cell death pathways in photodynamic therapy of cancer[J]. Cancers (Basel), 2011, 3(2):2516-2539.
21. LUO Ting. In vitro studies of improvement in treatment efficiency of photodynamic therapy of cancers through near-infrared bioluminescent activation[D]. Canada:University of Waterloo, 2014.

Journal of Biomedical Engineering

Induction of Apoptosis of Human Cisplatin-resistance Lung Cancer Cells with MPPa-photodynamic Therapy

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