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Abstract
Hepatocellular carcinoma (HCC) is one of the most common types of human malignancy worldwide, which is becoming increasingly resistant to traditional drug treatments. Puerarin combined with 5-fluorouracil (5-FU) may be a useful treatment for liver cancer. The primary aim of the present study was to determine whether combined treatment with 5-FU and puerarin is more effective against the hepatocellular carcinoma (HCC) cell line, SMMC7721, than treatment with 5-FU or puerarin alone. The growth inhibition of SMMC7721 cells by puerarin or 5-FU alone or in combination was determined by the Cell Counting Kit-8 assay, in vitro. Apoptotic morphological features and the percentage of apoptotic cells were detected using Hoechst 33258 staining and an Annexin V/PI apoptosis kit, respectively. In addition, a tumor xenograft model was established in nude mice using SMMC7721 cells. Puerarin and 5-FU alone or in combination were injected into the mice, and the inhibition of tumor growth was evaluated by monitoring tumor volume and weight. Treatment with 6,400 or 640 μM 5-FU resulted in growth inhibition of 95.56±0.81 and 75.91±3.54%, respectively. The combination index values were <1 when the fraction of affected cells was between 0.2555 and 0.7420. Furthermore, the percentage of apoptotic cells was markedly increased in the combined treatment group when compared with that of the individual treatment groups, in vitro and in vivo. Individual treatment with puerarin resulted in a tumor volume inhibition rate (IR) of 70.58% and a tumor weight IR of 46.20%. Treatment with 5-FU was found to decrease the tumor volume by 76.26% and tumor weight by 49.86%. In the combined treatment group, the tumor volume and weight IRs were 93.11 and 75.21%, respectively. A marked increase in the inhibition of tumor growth and the number of apoptotic cells in response to combined treatment with puerarin and 5-FU was identified with no observed liver or renal toxicity. These results suggest that puerarin and 5-FU exhibit a synergistic treatment effect on the HCC SMMC7721 cell line.
Highlights
Hepatocellular carcinoma (HCC) is the sixth most common type of human malignancy worldwide [1] and one of the most common types of malignant tumor in China
A marked increase in the inhibition of tumor growth and the number of apoptotic cells in response to combined treatment with puerarin and 5‐FU was identified with no observed liver or renal toxicity. These results suggest that puerarin and 5‐FU exhibit a synergistic treatment effect on the HCC SMMC7721 cell line
Data are presented as inhibition rate (%) = (1 - mean of tumor volume from the experimental group/mean of tumor volume for the control) x100 (n=6). aP
Summary
Hepatocellular carcinoma (HCC) is the sixth most common type of human malignancy worldwide [1] and one of the most common types of malignant tumor in China. Chemotherapy may be used to treat HCC; traditional systemic chemotherapy exhibits a low curative rate for liver cancer due to its high number of toxic effects, and is not widely accepted. Treatments combining several chemotherapeutic or chemopreventive agents have been used as they enhance the treatment effect and reduce drug toxicity. 5‐FU is commonly used in advanced‐stage HCC chemotherapy, alone or in combination with other drugs. Resistance to 5‐FU is a key cause of chemotherapy failure in advanced‐stage HCC [7] and, it is important to identify novel chemotherapeutic agents with high therapeutic efficacy. The combination of novel chemotherapeutic agents with existing drugs may enhance the efficacy of liver cancer therapy
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