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2018 ; 10
(2
): 334-351
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High-voltage pulsed electric field plus photodynamic therapy kills breast cancer
cells by triggering apoptosis
#MMPMID29511429
Zhang H
; Liu K
; Xue Z
; Yin H
; Dong H
; Jin W
; Shi X
; Wang H
; Wang H
Am J Transl Res
2018[]; 10
(2
): 334-351
PMID29511429
show ga
This study evaluated the effects and mechanism of action of combining
irreversible electroporation (IRE) and photodynamic therapy (PDT) in breast
cancer cells in vitro and in vivo. Jin's formula was used to assess killing
efficacy of different IRE+PDT dosing combinations in breast cancer MCF-7 cells.
Flow cytometry, high-content imaging, and confocal laser scanning microscopy were
used to detect apoptosis. qRT-PCR and western blotting were used to evaluate
expression of apoptosis-related genes and proteins. IRE+PDT combination therapy
was administered to BALB/C mice with breast cancer tumors in vivo; tumor size was
used to assess treatment efficacy. Killing mechanisms were examined using
transmission electron microscopy and immunohistochemistry. We found that IRE+PDT
combination therapy produced significant synergistic killing effects in breast
cancer cells (highest Jin q value of 1.32). Early apoptosis rates were
significantly higher in the IRE+PDT group (16.0%) than in IRE-alone (7.6%) and
PDT-alone (4.6%) groups (P<0.05). qRT-PCR showed higher Caspase-1, -3, -5, -6,
-7, -8, and -9 and TNFRSF1A expression with IRE+PDT than with control. Western
blots showed increased cleaved Caspase-3, -7, and -9, and PARP levels in the
IRE+PDT group. In vivo tumor suppression rate for IRE (1200 V)+PDT (10 mg/kg) was
68.3%. Combination therapy produced the most obvious apoptosis effects. Compared
with controls, the IRE+PDT group exhibited lower new blood vessel (VEGF, CD31),
metastasis (TGF-?), and cell proliferation (Ki-67) indicators and higher
inflammation indicator (TNF-?) 1 day post-treatment. Thus, combining IRE and PDT
enhanced their anti-tumor effects in breast cancer, and apoptosis played a key
role in this process.