Abstract
BackgroundSaikosaponin-d (SSd), a monomer terpenoid purified from the Chinese herbal drug Radix bupleuri, has multiple effects, including anticancer properties. However, the effect of SSd on tumors exposed to radiation is largely unknown. To investigate the radiosensitizing effect of SSd and its possible mechanism, we combined SSd with radiation therapy to treat SMMC-7721 hepatocellular carcinoma cells under oxia and hypoxia.MethodsCell growth, apoptosis, and cell cycle distribution were examined after treatment with SSd alone, radiation alone, and their combinations under oxia and hypoxia. The protein and mRNA levels of p53, Bcl2, and BAX were measured using western blot analysis and RT-PCR, respectively.ResultsTreatment with SSd alone and radiation alone inhibited cell growth and increased apoptosis rate at the concentration used. These effects were enhanced when SSd was combined with radiation. Moreover, SSd potentiated the effects of radiation to induce G0/G1 arrest in SMMC-7721 cells, and reduced the G2/M-phase population under hypoxia. However, under oxia, SSd only potentiated the effects of radiation to induce G0/G1 arrest, but not G2/M-phase arrest. These effects of SSd alone, radiation alone, and their combination, were accompanied by upregulated expression of p53 and BAX and downregulation of Bcl2 expression under oxia and hypoxia.ConclusionSSd potentiates the effects of radiation on SMMC-7721 cells; thus, it is a promising radiosensitizer. The radiosensitizing effect of SSd may contribute to its effect on the G0/G1 and G2/M checkpoints of the cell cycle.
Highlights
Saikosaponin-d (SSd), a monomer terpenoid purified from the Chinese herbal drug Radix bupleuri, has multiple effects, including anticancer properties
We found that 1 μg/mL SSd did not significantly inhibit the hepatoma cells under oxia and hypoxia
Irradiation followed by treatment with 1 μg/mL SSd increased the inhibition rate from 17.9 ± 3.42% to 23.1 ± 3.85%; under hypoxia, the inhibition rate increased from 12.8 ± 3.01% to 27.8 ± 4.52%
Summary
Saikosaponin-d (SSd), a monomer terpenoid purified from the Chinese herbal drug Radix bupleuri, has multiple effects, including anticancer properties. The effect of SSd on tumors exposed to radiation is largely unknown. To investigate the radiosensitizing effect of SSd and its possible mechanism, we combined SSd with radiation therapy to treat SMMC-7721 hepatocellular carcinoma cells under oxia and hypoxia. Primary hepatocellular carcinoma (HCC), which comprises 90% of all malignant tumors that develop in the liver, is one of the most devastating human malignancies: it can cause death within a few months unless treated properly [1,2]. To overcome the hypoxic resistance, several approaches have been developed over several decades to alter the hypoxic status of cancer cells during radiation therapy. Numerous new hypoxic radiosensitizers have recently been developed and some have even been clinically evaluated [6].
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