Chinese researchers discovered that anlotinib, a multitarget tyrosine kinase inhibitor, is effective in inhibiting the growth of intrahepatic cholangiocarcinoma (ICC) cell lines when used in combination with the chemotherapy drug gemcitabine, according to a study published in the Journal of Clinical Laboratory Analysis. 

Surgical resection remains the only curative option for ICC, but 5-year survival rates are a mere 30% to 35%. There is an urgent need to develop drugs other than chemotherapy medications that can improve clinical outcomes. 

Anlotinib is a promising drug already approved for use in non-small cell lung cancer. It works by suppressing tumor angiogenesis and impeding proliferation signaling pathways. Studies suggest that on its own, it has limited efficacy; however, it can produce more potent antitumor effects when used in combination with chemotherapy drugs. 

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Researchers set out to study if that was indeed the case. They employed the use of 2 ICC cell lines, HCC-9810 and RBE cells. To study cell viability, Cell Counting Kit-8 (CCK8) was used, while flow cytometry was used to study cell cycle arrest and apoptosis. Western blotting was performed to study the protein expression rates of cleaved PARP/PARP and cleaved caspase-3/caspase-3. 

The results showed that on its own, anlotinib inhibited ICC cell lines in vitro; the same was true for gemcitabine as a standalone drug. However, when combined, these 2 drugs produced powerful synergistic antitumor effects. Together they promoted the apoptosis of ICC cell lines and arrested the G0/G1 phase cell cycle. In addition, this combination of drugs increased the protein expression rates of cleaved PARP/PARP and cleaved caspase-3/caspase-3.

At present, research investigating the combination of targeted therapy with chemotherapy for ICC is limited. The synergistic effects of combination therapy as described in this study may produce better clinical outcomes for patients with ICC, though more studies are needed to verify these results.


Fan S, Ge Y, Liu J, et al. Combination of anlotinib and gemcitabine promotes the G0/G1 cell cycle arrest and apoptosis of intrahepatic cholangiocarcinoma in vitro. J Clin Lab Anal. Published online August 30, 2021. doi:10.1002/jcla.23986