Combination chemotherapy of doxorubicin and paclitaxel for hepatocellular carcinoma in vitro and in vivo

Jin, Cheng; Li, Haimin; He, Yong; He, Min; Bai, Ling; Cao, Yunxin; Song, Wenjie; Dou, Kefeng

doi:10.1007/s00432-009-0658-5

Cited by 50 publications

(35 citation statements)

References 26 publications

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“…The downmodulation of VEGF expression as reported here may also explain the antiangiogenic potential of this chalcone that needs further investigation. Doxorubicin and paclitaxel are commonly used chemotherapeutic drugs for the treatment of HCC (54). We further show that butein substantially potentiates the apoptotic effect of doxorubicin and paclitaxel in HCC cells as evident by esterase staining and can be used in combination with existing chemotherapeutic drugs for the treatment of HCC.…”

Section: Discussionmentioning

confidence: 58%

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Suppression of Signal Transducer and Activator of Transcription 3 Activation by Butein Inhibits Growth of Human Hepatocellular Carcinoma In Vivo

Rajendran

Ong

Chen

et al. 2011

Clinical Cancer Research

129

100

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Purpose: Hepatocellular carcinoma (HCC) is the fifth most common malignancy worldwide and the third cause of global cancer mortality. Increasing evidence suggest that STAT3 is a critical mediator of oncogenic signaling in HCC and controls the expression of several genes involved in proliferation, survival, metastasis, and angiogenesis. Thus, the novel agents that can suppress STAT3 activation have potential for both prevention and treatment of HCC.Experimental Design: The effect of butein on STAT3 activation, associated protein kinases, STAT3-regulated gene products, cellular proliferation, and apoptosis was investigated. The in vivo effect of butein on the growth of human HCC xenograft tumors in male athymic nu/nu mice was also examined.Results: We tested an agent, butein, for its ability to suppress STAT3 activation in HCC cells and nude mice model along with prospectively testing the hypothesis of STAT3 inhibition in a virtual predictive functional proteomics tumor pathway technology platform. We found that butein inhibited both constitutive and inducible STAT3 activation in HCC cells. The suppression was mediated through the inhibition of activation of upstream kinases c-Src and Janus-activated kinase 2. Butein inhibited proliferation and significantly potentiated the apoptotic effects of paclitaxel and doxorubicin in HCC cells. When administered intraperitoneally, butein inhibited the growth of human HCC xenograft tumors in male athymic nu/nu mice.Conclusions: Overall, cumulative results from experimental and predictive studies suggest that butein exerts its antiproliferative and proapoptotic effects through suppression of STAT3 signaling in HCC both in vitro and in vivo.

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Section: Discussionmentioning

confidence: 58%

“…Among chemotherapeutic agents, doxorubicin, an anthracycline antibiotic, and paclitaxel, a mitotic inhibitor, have been used for HCC treatment (54). We examined whether butein can potentiate the effect of these drugs.…”

Section: Butein Potentiates the Apoptotic Effect Of Doxorubicin And Pmentioning

confidence: 99%

Suppression of Signal Transducer and Activator of Transcription 3 Activation by Butein Inhibits Growth of Human Hepatocellular Carcinoma In Vivo

Rajendran

Ong

Chen

et al. 2011

Clinical Cancer Research

129

100

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“…Chemotherapy with these 2 agents has been of interest in hepatocellular carcinoma 24 and lung cancer, 25 and both agents, in contrast to cisplatin, are ligands of P-glycoprotein (P-gp). P-gp is a plasma membrane efflux pump that is a component of cancer cell chemoresistance and is subject to inhibition by tetrac.…”

Section: Introductionmentioning

confidence: 99%

Targeted delivery of paclitaxel and doxorubicin to cancer xenografts via the nanoparticle of nano-diamino-tetrac

Sudha

Bharali

Yalçın

et al. 2017

IJN

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The tetraiodothyroacetic acid (tetrac) component of nano-diamino-tetrac (NDAT) is chemically bonded via a linker to a poly(lactic- co -glycolic acid) nanoparticle that can encapsulate anticancer drugs. Tetrac targets the plasma membrane of cancer cells at a receptor on the extracellular domain of integrin αvβ3. In this study, we evaluate the efficiency of NDAT delivery of paclitaxel and doxorubicin to, respectively, pancreatic and breast cancer orthotopic nude mouse xenografts. Intra-tumoral drug concentrations were 5-fold (paclitaxel; P <0.001) and 2.3-fold (doxorubicin; P <0.01) higher than with conventional systemic drug administration. Tumor volume reductions reflected enhanced xenograft drug uptake. Cell viability was estimated by bioluminescent signaling in pancreatic tumors and confirmed an increased paclitaxel effect with drug delivery by NDAT. NDAT delivery of chemotherapy increases drug delivery to cancers and increases drug efficacy.

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“…To keep a commensurable inhibitory effect, the loaded amount of DOX in MMSNs was controlled to be approximately 90 µg/mg, which was chosen based on the half maximal inhibitory concentration (IC 50 ) of free drug in A549 cells in our pilot experiment (data not shown) and published studies. 52 The ratio of DOX to PTX was scaled to 9:1 (m:m) by adopting our sequential and tunable loading strategy. Similarly, for the DOX-RAPA combination, the ratio was set to be 1:1 (m:m).…”

Section: Improved Cancer Cell Killing and Inhibition By The Multidrugmentioning

confidence: 99%

“…Similar effects were also reported by Chang and colleagues. 44 On the other hand, the DOX-PTX combination was reported to have increased antitumor activity against solid tumors, eg, lung, colon, breast, and liver cancer, 52,54 while the use of the RAPA-DOX combination has yet to be documented in clinical applications. Herein we demonstrated notable synergistic anticancer effects for both DOX-PTX and DOX-RAPA combinations.…”

Section: Improved Cancer Cell Killing and Inhibition By The Multidrugmentioning

confidence: 99%

Delivering hydrophilic and hydrophobic chemotherapeutics simultaneously by magnetic mesoporous silica nanoparticles to inhibit cancer cells

Liu¹,

Zhang²,

Sun³

et al. 2012

IJN

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Using nanoparticles to deliver chemotherapeutics offers new opportunities for cancer therapy, but challenges still remain when they are used for the delivery of multiple drugs, especially for the synchronous delivery of hydrophilic and hydrophobic drugs in combination therapies. In this paper, we developed an approach to deliver hydrophilic-hydrophobic anticancer drug pairs by employing magnetic mesoporous silica nanoparticles (MMSNs). We prepared 50 nm-sized MMSNs with uniform pore size and evaluated their capability for the loading of two combinations of chemotherapeutics, namely doxorubicin-paclitaxel and doxorubicinrapamycin, by means of sequential adsorption from the aqueous solution of doxorubicin and nonaqueous solutions of paclitaxel or rapamycin. Experimental results showed that the present strategy successfully realized the co-loading of hydrophilic and hydrophobic drugs with high-loading content and widely tunable ratio range. We elaborate on the theory behind the molecular interaction between the silica hydroxyl groups and drug molecules, which underlie the controllable loading, and the subsequent release of the drug pairs. Then we demonstrate that the multidrug-loaded MMSNs could be easily internalized by A549 human pulmonary adenocarcinoma cells, and produce enhanced tumor cell apoptosis and growth inhibition as compared to single-drug loaded MMSNs. Our study thus realized simultaneous and dose-tunable delivery of hydrophilic and hydrophobic drugs, which were endowed with improved anticancer efficacy. This strategy could be readily extended to other chemotherapeutic combinations and might have clinically translatable significance.

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Combination chemotherapy of doxorubicin and paclitaxel for hepatocellular carcinoma in vitro and in vivo

Abstract: The study may provide a new combination of cytotoxic drugs for HCC chemotherapy.

Cited by 50 publications

References 26 publications

Suppression of Signal Transducer and Activator of Transcription 3 Activation by Butein Inhibits Growth of Human Hepatocellular Carcinoma In Vivo

Suppression of Signal Transducer and Activator of Transcription 3 Activation by Butein Inhibits Growth of Human Hepatocellular Carcinoma In Vivo

Targeted delivery of paclitaxel and doxorubicin to cancer xenografts via the nanoparticle of nano-diamino-tetrac

Delivering hydrophilic and hydrophobic chemotherapeutics simultaneously by magnetic mesoporous silica nanoparticles to inhibit cancer cells

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