Poster Presentation 28th Lorne Cancer Conference 2016

Targeting liver cancer stem cells with aptamer-drug conjugate (#281)

Wang Yin 1 , Dongxi Xiang 1 , Sarah Shigdar 1 , Wei Duan 1
  1. School of Medicine, Deakin University, Geelong, VIC, Australia

It has been proposed that tumours are organised in a hierarchy of heterogeneous cell population in which only a small subset of cells, termed cancer stem cells (CSCs), have the ability to drive cancer growth and metastasis1. In the case of hepatocellular carcinoma (HCC), it is well established that CD133+ HCC cells have higher capacity for tumourigenecity and they confer the chemoresistance and radioresistance2-4. Therefore, it becomes crucial to target the CSC population within HCC to eradicate the source of cancer. Our lab has developed an RNA aptamer against the CSC marker CD1335. This aptamer is conjugated with doxorubicin (Dox), which is one of the most potent chemotherapeutic agent and is widely used for the treatment of HCC6,7. We hypothesised that the aptamer-Dox conjugate could be specifically internalised into and kill CD133+ HCC CSC cells. We investigated the therapeutic potential of aptamer-Dox conjugate by assessing the cellular uptake and its capacity to inhibit self-renewal of liver CSCs. The results showed that the CD133 aptamer selectively delivered Dox into human HCC Huh7 and PLC/PRF/5 cells (observed by confocal microscopy). Limiting dilution analysis revealed that treatment of Huh7 and PLC/PRF/5 cells with CD133 aptamer-Dox conjugate lead to a significant decrease in CSC frequency compared with cells treated with free Dox. In conclusion, these studies indicate CD133 aptamer-Dox conjugate as a potential liver CSC inhibitor.

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