title: Energy controllable steep pulse (ECSP) treatment suppresses tumor growth in rats implanted with Walker 256 carcinosarcoma cells through apoptosis and an antitumor immune response.
abstract: Electrochemotherapy has been widely used for the treatment of solid tumors, although the underlying mechanism remains unclear. We aimed to investigate the effects of energy controllable steep pulse (ECSP) on the regulation of tumor growth and apoptosis in rats implanted with Walker 256 carcinosarcoma cells. A rat tumor model was established by injection of Walker 256 carcinosarcoma cells into the inguinal area. H&E staining, transmission electron microscopy, and the TUNEL assay were used to detect apoptosis. Concanavalin A-induced lymphocyte transformation and MTT assays were used to assess lymphocyte proliferation. ELISA was used to determine serum cytokine levels. After 2 weeks of ECSP treatment, tumor growth in rats was effectively suppressed, while tumor cell apoptosis was significantly induced compared to the control tumor group. Moreover, ECSP treatment enhanced proliferation and activation of lymphocytes and natural killer (NK) cells. Serum IL-2 and IFN-gamma levels were significantly decreased, and IL-4 and 1-10 levels dramatically increased in rats with control tumors compared to rats without tumors and lacking treatment (p < 0.05). In contrast, ECSP treatment increased IL-2 and IFN-gamma levels, but reduced IL-4 and IL-10 levels to normal values. Moreover, ECSP also increased TNF-alpha production, possibly from peritoneal microphages. Our current study demonstrates that ECSP treatment is able to effectively reduce tumors in rats via induction of apoptosis and activation of the rat antitumor immune response. These data provide insightful information for the future application of ECSP-based electrochemotherapy in clinical trials against solid tumors.
authors.affiliation: Department of Obstetrics and Gynecology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Luo
authors.forename: Jiang-chuan
authors.initials: JC
authors.lastname: Sun
authors.forename: Feng
authors.initials: F
authors.lastname: Liu
authors.forename: Li-Na
authors.initials: LN
authors.lastname: Hu
authors.forename: Xiao-Jing
authors.initials: XJ
authors.lastname: Dong
authors.forename: Di-Na
authors.initials: DN
authors.lastname: Sun
authors.forename: Jin
authors.initials: J
authors.lastname: Xiao
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002279:Carcinoma 256, Walker / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D016207:Cytokines / Q000276:immunology; D053672:Electrochemotherapy / Q000295:instrumentation / Q000379:methods*; D004574:Electromagnetic Fields; D005260:Female; D007694:Killer Cells, Natural / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology; D008297:Male; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000517:prevention & control; D051381:Rats; D017208:Rats, Wistar; D019139:Tumor Escape / Q000276:immunology*
chemical_list: D016207:Cytokines