Enhancement of anti-tumor effects of 5-fluorouracil on hepatocellular carcinoma by low-intensity ultrasound

Hu, Zheng; Lv, Guixiang; Li, Yongning; Li, Enze; Li, Haixia; Zhou, Qi; Yang, Bin; Cao, Wenwu

doi:10.1186/s13046-016-0349-4

Cited by 47 publications

(45 citation statements)

References 37 publications

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“…Sorafenib, as only one drug approved to treat advanced HCC, can prolong poor overall survival by less than 3 months . In previous work, we enhanced the sensitivity of HCC to chemotherapy by the ultrasound, but it is not enough . Therefore, there is an urgent need to clarify the underlying mechanism and establish better therapeutic strategies for HCC.…”

Section: Discussionmentioning

confidence: 99%

miR‐320a regulates high mobility group box 1 expression and inhibits invasion and metastasis in hepatocellular carcinoma

Wu²,

Wang

et al. 2017

Liver International

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Section: Discussionmentioning

confidence: 99%

miR‐320a regulates high mobility group box 1 expression and inhibits invasion and metastasis in hepatocellular carcinoma

Wu²,

Wang

et al. 2017

Liver International

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“…reveal the role of CD317 in protecting tumor cells from nutrient deficient-induced apoptosis and the mechanism that CD317 plays an inhibitory role in the mitochondria-AIF axis, suggesting that CD317 silencing could be a considerable approach for combined cancer therapies. Recently, Zheng Hu et al reported low-intensity ultrasound combined with 5-FU produced much enhanced synergistic anti-tumor effects via enhanced mitochondria-cytochrome c-caspase cascades [ 36 ]. However, the anti-tumor effects could only be partially rescued by pan-caspase inhibitor, strongly suggesting that another mitochondrial pro-apoptotic factor such as AIF may be involved in this process.…”

Section: Discussionmentioning

confidence: 99%

CD317 Promotes the survival of cancer cells through apoptosis-inducing factor

Zhang

Chen

et al. 2016

J Exp Clin Cancer Res

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BackgroundLow nutrient environment is a major obstacle to solid tumor growth. However, many tumors have developed adaptive mechanisms to circumvent the requirement for exogenous growth factors.MethodsHere we used siRNA interference or plasmid transfection techniques to knockdown or enhance CD317 expression respectively, in mammalian cancer cells, and subjected these CD317-manipulated cells to serum deprivation to study the role of CD317 on stress-induced apoptosis and the underlying mechanism.ResultsWe report that CD317, an innate immune gene overexpressed in human cancers, protected cancer cells against serum deprivation-induced apoptosis. In tumor cells, loss of CD317 markedly enhanced their susceptibility to serum deprivation-induced apoptosis with no effect on autophagy or caspase activation, indicating an autophagy- and caspase-independent mechanism of CD317 function. Importantly, CD317 knockdown in serum-deprived tumor cells impaired mitochondria function and subsequently promoted apoptosis-inducing factor (AIF) release and nuclear translocation but had little effect on mitochondrial and cytoplasmic distributions of cytochrome C, a pro-apoptotic factor released from mitochondria that initiates caspase processing in response to death stimuli. Furthermore, overexpression of CD317 in HEK293T cells inhibits serum deprivation-induced apoptosis as well as the release and nuclear accumulation of AIF.ConclusionOur data suggest that CD317 functions as an anti-apoptotic factor through the mitochondria-AIF axis in malnourished condition and may serve as a potential drug target for cancer therapy.Electronic supplementary materialThe online version of this article (doi:10.1186/s13046-016-0391-2) contains supplementary material, which is available to authorized users.

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“…The present results suggested that liuS may enhance Hcc cell apoptosis in combination with chemotherapy. a previous study reported that treatment with liuS increases intracellular roS accumulation (21). Subsequently, the association between roS and liuS-induced apoptosis was investigated.…”

Section: Dox Combined With Lius Promotes Apoptosis Of Hcc Cellsmentioning

confidence: 98%

Low‑intensity ultrasound enhances the antitumor effects of doxorubicin on hepatocellular carcinoma cells through the ROS‑miR‑21‑PTEN axis

Xia¹,

Zeng²,

Zheng

2020

Mol Med Report

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Hepatocellular carcinoma (Hcc) is a type of liver cancer and is a leading cause of cancer-associated mortality. in china, ~466,000 patients are diagnosed with Hcc and it is responsible for ~422,000 cases of mortality each year. Surgery is the most effective treatment available; however it is only suitable for patients with early-stage Hcc. chemotherapy has been confirmed as a necessary treatment for patients with advanced Hcc, although drug resistance may limit its clinical outcome. low intensity ultrasound (liuS) represents a novel therapeutic approach to treat patients with Hcc; however, its underlying molecular mechanism remains unclear. in the present study, cell viability, apoptosis and reactive oxygen species (roS) generation were determined via cell counting Kit-8, flow cytometry and 2',7'-dichlorofluorescein diacetate assays, respectively. The expression of mirna in Hcc cells following exposure to liuS and doxorubicin (dox) was analyzed using a microarray and reverse transcription-quantitative polymerase chain reaction analysis. it was revealed treatment with liuS in combination with dox was able to induce apoptosis of Huh7 cells, increasing the intracellular levels of reactive oxygen species (roS) and malondialdehyde. Glutathione peroxidase and superoxide dismutase 1 are roS-scavenging enzymes, which serve important roles in the oxidative balance, preventing oxidative stress. The protein expression levels of these two enzymes were significantly decreased following treatment with liuS combined with dox. The present results suggested that liuS may decrease dox resistance in Hcc cells and that liuS may be combined with chemotherapy to treat Hcc. By performing microarray analysis, the expression levels of microrna-21 (mir-21) were decreased following treatment with liuS combined with dox. Functional experiments showed that knockdown of mir-21 enhanced the antitumor activity of dox, whereas overexpression of mir-21 reversed these effects. Phosphatase and tensin homolog (PTen), a well-known tumor suppressor, was revealed to be a direct target of mir-21, and its translation was suppressed by mir-21. Finally, it was determined that combined treatment of liuS and dox induced anticancer effects by blocking the activation of the aKT/mTor pathway, as demonstrated by the downregulation of phosphorylated (p-)aKT and p-mTor; n-acetylcysteine, a general roS inhibitor reversed the suppressive effects on the aKT/mTor pathway mediated by liuS and dox. collectively, the present results suggested that liuS increased cell sensitivity to dox via the roS/mir-21/PTen pathway. chemotherapy combined with liuS may represent a novel effective therapeutic strategy to treat patients with advanced Hcc.

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Enhancement of anti-tumor effects of 5-fluorouracil on hepatocellular carcinoma by low-intensity ultrasound

Cited by 47 publications

References 37 publications

miR‐320a regulates high mobility group box 1 expression and inhibits invasion and metastasis in hepatocellular carcinoma

miR‐320a regulates high mobility group box 1 expression and inhibits invasion and metastasis in hepatocellular carcinoma

CD317 Promotes the survival of cancer cells through apoptosis-inducing factor

Low‑intensity ultrasound enhances the antitumor effects of doxorubicin on hepatocellular carcinoma cells through the ROS‑miR‑21‑PTEN axis

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