Low Temperature Plasma Suppresses Lung Cancer Cells Growth Via VEGF/VEGFR2/RAS/ERK Axis

Overview

Journal Molecules

Publisher MDPI

Specialty Biology

Date 2022 Sep 23

PMID 36144670

Authors

Yuanyuan Zhou

Yan Zhang

Jie Bao

Jinwu Chen

Wencheng Song

Affiliations

Soon will be listed here.

Abstract

Low temperature plasma (LTP) is a promising cancer therapy in clinical practice. In this study, dielectric barrier discharge plasma with helium gas was used to generate LTP. Significant increases in extracellular and intracellular reactive species were found in lung cancer cells (CALU-1 and SPC-A1) after LTP treatments. Cells viability and apoptosis assays demonstrated that LTP inhibited cells viability and induced cells death, respectively. Moreover, Western blotting revealed that the growth of CALU-1 cells was suppressed by LTP via the VEGF/VEGFR2/RAS/ERK axis for the first time. The results showed that LTP-induced ROS and RNS could inhibit the growth of lung cancer cells via VEGF/VEGFR2/RAS/ERK axis. These findings advance our understanding of the inhibitory mechanism of LTP on lung cancer and will facilitate its clinical application.

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References

Ramakrishnan V, Timm M, Haug J, Kimlinger T, Halling T, Wellik L . Sorafenib, a multikinase inhibitor, is effective in vitro against non-Hodgkin lymphoma and synergizes with the mTOR inhibitor rapamycin. Am J Hematol. 2011; 87(3):277-83. PMC: 3465673. DOI: 10.1002/ajh.22263. View

Chen G, Chen Z, Wen D, Wang Z, Li H, Zeng Y . Transdermal cold atmospheric plasma-mediated immune checkpoint blockade therapy. Proc Natl Acad Sci U S A. 2020; 117(7):3687-3692. PMC: 7035610. DOI: 10.1073/pnas.1917891117. View

von Woedtke T, Schmidt A, Bekeschus S, Wende K, Weltmann K . Plasma Medicine: A Field of Applied Redox Biology. In Vivo. 2019; 33(4):1011-1026. PMC: 6689367. DOI: 10.21873/invivo.11570. View

Hilger R, Scheulen M, Strumberg D . The Ras-Raf-MEK-ERK pathway in the treatment of cancer. Onkologie. 2003; 25(6):511-8. DOI: 10.1159/000068621. View

Song Y, Dai F, Zhai D, Dong Y, Zhang J, Lu B . Usnic acid inhibits breast tumor angiogenesis and growth by suppressing VEGFR2-mediated AKT and ERK1/2 signaling pathways. Angiogenesis. 2012; 15(3):421-32. DOI: 10.1007/s10456-012-9270-4. View

Wang Q, Zheng X, Yang L, Shi F, Gao L, Zhong Y . Reactive oxygen species-mediated apoptosis contributes to chemosensitization effect of saikosaponins on cisplatin-induced cytotoxicity in cancer cells. J Exp Clin Cancer Res. 2010; 29:159. PMC: 3006358. DOI: 10.1186/1756-9966-29-159. View

Semmler M, Bekeschus S, Schafer M, Bernhardt T, Fischer T, Witzke K . Molecular Mechanisms of the Efficacy of Cold Atmospheric Pressure Plasma (CAP) in Cancer Treatment. Cancers (Basel). 2020; 12(2). PMC: 7072164. DOI: 10.3390/cancers12020269. View

Watanabe H, Ichihara E, Kayatani H, Makimoto G, Ninomiya K, Nishii K . VEGFR2 blockade augments the effects of tyrosine kinase inhibitors by inhibiting angiogenesis and oncogenic signaling in oncogene-driven non-small-cell lung cancers. Cancer Sci. 2021; 112(5):1853-1864. PMC: 8088971. DOI: 10.1111/cas.14801. View

Chernets N, Kurpad D, Alexeev V, Rodrigues D, Freeman T . Reaction Chemistry Generated by Nanosecond Pulsed Dielectric Barrier Discharge Treatment is Responsible for the Tumor Eradication in the B16 Melanoma Mouse Model. Plasma Process Polym. 2017; 12(12):1400-1409. PMC: 5667549. DOI: 10.1002/ppap.201500140. View

10.

Zhao Z, Zhang D, Wu F, Tu J, Song J, Xu M . Sophoridine suppresses lenvatinib-resistant hepatocellular carcinoma growth by inhibiting RAS/MEK/ERK axis via decreasing VEGFR2 expression. J Cell Mol Med. 2020; 25(1):549-560. PMC: 7810959. DOI: 10.1111/jcmm.16108. View

11.

Kalghatgi S, Kelly C, Cerchar E, Torabi B, Alekseev O, Fridman A . Effects of non-thermal plasma on mammalian cells. PLoS One. 2011; 6(1):e16270. PMC: 3025030. DOI: 10.1371/journal.pone.0016270. View

12.

Kaushik N, Kaushik N, Yoo K, Uddin N, Kim J, Lee S . Data on combination effect of PEG-coated gold nanoparticles and non-thermal plasma inhibit growth of solid tumors. Data Brief. 2016; 9:318-23. PMC: 5026707. DOI: 10.1016/j.dib.2016.08.059. View

13.

Apte R, Chen D, Ferrara N . VEGF in Signaling and Disease: Beyond Discovery and Development. Cell. 2019; 176(6):1248-1264. PMC: 6410740. DOI: 10.1016/j.cell.2019.01.021. View

14.

Guerrero-Preston R, Ogawa T, Uemura M, Shumulinsky G, Valle B, Pirini F . Cold atmospheric plasma treatment selectively targets head and neck squamous cell carcinoma cells. Int J Mol Med. 2014; 34(4):941-6. PMC: 4152136. DOI: 10.3892/ijmm.2014.1849. View

15.

Huang M, Huang B, Li G, Zeng S . Apatinib affect VEGF-mediated cell proliferation, migration, invasion via blocking VEGFR2/RAF/MEK/ERK and PI3K/AKT pathways in cholangiocarcinoma cell. BMC Gastroenterol. 2018; 18(1):169. PMC: 6220519. DOI: 10.1186/s12876-018-0870-3. View

16.

Ahmed M, Liu Z, Afzal K, Weeks D, Lobo S, Kruskal J . Radiofrequency ablation: effect of surrounding tissue composition on coagulation necrosis in a canine tumor model. Radiology. 2004; 230(3):761-7. DOI: 10.1148/radiol.2303021801. View

17.

Chatterjee S, Rhee Y, Chung P, Ge R, Ahn J . Sulforaphene Enhances The Efficacy of Photodynamic Therapy In Anaplastic Thyroid Cancer Through Ras/RAF/MEK/ERK Pathway Suppression. J Photochem Photobiol B. 2018; 179:46-53. DOI: 10.1016/j.jphotobiol.2017.12.013. View

18.

Xiong W, Xu Q, Xu Y, Sun C, Li N, Zhou L . Stereotactic body radiation therapy for post-pulmonary lobectomy isolated lung metastasis of thoracic tumor: survival and side effects. BMC Cancer. 2014; 14:719. PMC: 4189164. DOI: 10.1186/1471-2407-14-719. View

19.

Wu S, Noren Hooten N, Freeman D, Mode N, Zonderman A, Evans M . Extracellular vesicles in diabetes mellitus induce alterations in endothelial cell morphology and migration. J Transl Med. 2020; 18(1):230. PMC: 7285586. DOI: 10.1186/s12967-020-02398-6. View

20.

Yan D, Wang Q, Malyavko A, Zolotukhin D, Adhikari M, Sherman J . The anti-glioblastoma effect of cold atmospheric plasma treatment: physical pathway v.s. chemical pathway. Sci Rep. 2020; 10(1):11788. PMC: 7366727. DOI: 10.1038/s41598-020-68585-z. View