Get access

Synergism of hydroxyapatite nanoparticles and recombinant mutant human tumour necrosis factor-α in chemotherapy of multidrug-resistant hepatocellular carcinoma

Authors

  • Gaopeng Li,

    1. Department of Ultrasound, the Second Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China
    2. Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China
    Search for more papers by this author
  • Shengli Dong,

    1. Department of General Surgery, the Second Affiliated Hospital, Shanxi Medical University, Taiyuan, Shanxi Province, China
    Search for more papers by this author
  • Junyuan Qu,

    1. Department of Galactophore Surgery, Shanxi Tumour Hospital, Taiyuan, Shanxi Province, China
    Search for more papers by this author
  • Zhengang Sun,

    1. Department of Ultrasound, the Second Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China
    Search for more papers by this author
  • Zhiyong Huang,

    1. Department of Ultrasound, the Second Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China
    Search for more papers by this author
  • Lu Ye,

    1. Infection Department, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China
    Search for more papers by this author
  • Huifang Liang,

    1. Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China
    Search for more papers by this author
  • Xi Ai,

    1. Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China
    Search for more papers by this author
  • Wanguang Zhang,

    1. Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China
    Search for more papers by this author
  • Xiaoping Chen

    1. Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China
    Search for more papers by this author

Correspondence
Xiaoping Chen, MD, PhD, FACS, Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
Tel: +86 27 83662599
Fax: +86 27 83662851
e-mail: chenxp@medmail.com.cn

Abstract

Background/Aims: Locoregional chemotherapy continues to be the mainstay for the treatment of unresectable hepatocellular carcinoma (HCC). One of the principal obstacles implicated in its unsuccessful therapy is multidrug resistance (MDR). Former studies have identified the multidrug-resistant nature and possible mechanisms of hepatoma cells both in vitro and in vivo. This work aimed to develop an effective strategy for the treatment of HCC with MDR.

Methods: The treatment was exploited to inhibit the MDR cells by co-administration of the recombinant mutant human tumour necrosis factor-α (rmhTNF-α), a sublethal dose of chemicals [adriamycin (ADM), mitomycin and 5-FU] and hydroxyapatite nanoparticles (nHAPs). Real-time quantitative reverse transcriptase-polymerase chain reaction and electrochemiluminescence Western blot were used to detect the expression of several related genes.

Results: The chemicals acted synergistically with rmhTNF-α and nHAP in suppressing the growth of hepatoma cells and inducing apoptosis of the cells, with the MDR phenotype reversed, as measured by intracellular ADM retention. Analysis of mRNA and protein revealed that rmhTNF-α inhibited the gene expression of XIAP, survivin, Ki67, PCNA, MDR1 and BCRP to some extent. Moreover, the inhibitory effects mentioned above could be as good or better than when nHAP is incorporated into the regimens.

Conclusions: rmhTNF-α was not only able to restore the chemotherapeutic sensitivity to HepG2/ADM, its xenograft model and clinical samples but also further inhibited the growth of these tumours by a combination of nHAP. These results strongly suggested that chemicals in combination with rmhTNF-α and nHAP may be beneficial for the local treatment of advanced HCC.

Ancillary