Research Papers:

Combretastatin-A4 phosphate improves the distribution and antitumor efficacy of albumin-bound paclitaxel in W256 breast carcinoma model

Meng Gao, Dongjian Zhang, Qiaomei Jin, Cuihua Jiang, Cong Wang, Jindian Li, Fei Peng, Dejian Huang, Jian Zhang and Shaoli Song _

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Oncotarget. 2016; 7:58133-58141. https://doi.org/10.18632/oncotarget.11249

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Meng Gao1,2, Dongjian Zhang1,2, Qiaomei Jin1,2, Cuihua Jiang1,2, Cong Wang3, Jindian Li3, Fei Peng1,2, Dejian Huang1,2, Jian Zhang1,2, Shaoli Song4

1Laboratory of Translational Medicine, Jiangsu Province Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, Jiangsu Province, P.R.China

2Laboratory of Translational Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, Jiangsu Province, P.R.China

3Department of Natural Medicinal Chemistry and State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, Jiangsu Province, P.R. China

4Department of Nuclear Medicine, Renji Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai 200127, P.R. China

Correspondence to:

Jian Zhang, email: [email protected]

Shaoli Song, email: [email protected]

Keywords: combretastatin-A-4 phosphate, interstitial fluid pressure, albumin-bound paclitaxel, tissue distribution, combination therapy

Received: February 15, 2016     Accepted: July 27, 2016     Published: August 12, 2016


Nanomedicine holds great promise for fighting against malignant tumors. However, tumor elevated interstitial fluid pressure (IFP) seriously hinders convective transvascular and interstitial transport of nanomedicines and thus damages its antitumor efficacy. In this study, combretastatin-A4 phosphate (CA4P) was utilized to reduce tumor IFP, and thereby to improve the intratumoral distribution and antitumor efficacy of nanoparticle albumin-bound paclitaxel (nab-paclitaxel). IFP was measured using the wick-in-needle method in tumors growing subcutaneously pretreatment and posttreatment with a single intravenous injection of CA4P. The tracing method of iodine 131 isotope was used for biodistribution analysis of nab-paclitaxel. Liquid chromatography coupled with tandem mass spectrometry was used to detect the intratumoral concentration of paclitaxel. Magnetic resonance imaging was applied to monitor tumor volume and ratios of necrosis. The tumor IFP continued to decline gradually over time following CA4P treatment, reaching approximately 31% of the pretreatment value by 1 h posttreatment. Biodistribution data indicated that both 131I-nab-paclitaxel and paclitaxel exhibited higher tumor uptake in CA4P + 131I-nab-paclitaxel group compared with I131-nab-paclitaxel group. Nab-paclitaxel combined with CA4Pshowed significant tumor growth inhibition and higher tumor necrosis ratio relative to PBS, CA4P and nab-paclitaxel group, respectively. In conclusion, CA4P improved the intratumoral distribution and antitumor efficacy of nab-paclitaxel in W256 tumor-bearing rats.

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