Tumor Biology

, Volume 37, Issue 1, pp 331–339 | Cite as

Imperatorin acts as a cisplatin sensitizer via downregulating Mcl-1 expression in HCC chemotherapy

  • Jianjian Hu
  • Changlong Xu
  • Bihuan Cheng
  • Lingxiang Jin
  • Jie Li
  • Yuqiang Gong
  • Wei Lin
  • Zhenzhen Pan
  • Chenwei Pan
Research Article


Acquisition of cisplatin resistance is the common and critical limitation for hepatocellular carcinoma (HCC) therapy. Our study was aimed to determine whether there were conditions under which the addition of imperatorin would reverse the resistance of HCC cells to cisplatin-based therapy. In this study, we found that addition of imperatorin significantly enhanced the cytotoxicity of cisplatin to HCC cells. Since the Mcl-1 was overexpressed in HCC cell lines (HepG2, HepG3B, PLC, Huh7) compared with normal liver cell line (L-O2), we found that the Mcl-1 expression was downregulated by imperatorin but not influenced by cisplatin in HCC cells. In addition, our results showed the combination of imperatorin and cisplatin induced apoptosis and ∆Ψm collapse more significantly compared with treatment of imperatorin or cisplatin alone. Furthermore, the imperatorin-induced sensitization for cisplatin-cytotoxicity to HCC cells was abolished by the transfection of Mcl-1 expression plasmid. Finally, we found that the addition of imperatorin significantly reversed the resistance to cisplatin in cisplatin-resistant HCC cells, which was Mcl-1 dependent. In summary, our study revealed that combination with imperatorin could enhance the antitumor activity of cisplatin via targeting Mcl-1 and reverse the resistance to cisplatin in HCC.


HCC Imperatorin Cisplatin Mcl-1 Apoptosis 



This work was supported by the Program of WenZhou Science and Technology Bureau (grant no. Y20140092)

Conflict of interest


Author contributions

CP designed the study. JH, CX, and BC wrote the manuscript. JH, LJ, and JL performed out the immunohistochemistry and the related statistical analysis. JH, YG, WL, and ZP carried out the cell culture and transfection, Western blot, RT-PCR, and flow cytometry. All authors approved the final version of the manuscript.

Supplementary material

13277_2015_3591_MOESM1_ESM.tif (931 kb)
Fig. Supplement The transfection efficiency of pcDNA3.1-Mcl-1 in HCC cells. (A) HepG2 cells and Huh7 cells were transfected with pcDNA3.1-Mcl-1 plasmid or its control. After 24 h incubation, the Mcl-1 mRNA level was detected by quantitative PCR. (B) Mcl-1 protein level was detected by western blot assay after the HepG2 and Huh7 cells were treated as above. (TIFF 931 kb)
13277_2015_3591_Fig6_ESM.gif (706 kb)
High Resolution (GIF 706 kb)


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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Jianjian Hu
    • 1
  • Changlong Xu
    • 2
  • Bihuan Cheng
    • 1
  • Lingxiang Jin
    • 3
  • Jie Li
    • 3
  • Yuqiang Gong
    • 1
  • Wei Lin
    • 3
  • Zhenzhen Pan
    • 4
  • Chenwei Pan
    • 3
  1. 1.Department of Anesthesiology, Critical Care and Pain MedicineThe Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical UniversityWenzhouChina
  2. 2.Department of GastroenterologyThe Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical UniversityWenzhou CityChina
  3. 3.Department of Infectious DiseaseThe Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical UniversityWenzhou CityChina
  4. 4.Department of Infectious DiseaseThe First Affiliated Hospital of Wenzhou Medical UniversityWenzhouChina

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