| Summary: | 碩士 === 國立中興大學 === 生命科學系所 === 101 === Hepatocellular carcinoma(HCC) is among the most lethal and prevalent cancers in human epidemiology. On the choice of drugs, Tetrahydrocurcumin has been demonstrated to be the major metabolite of curcumin.Curcumin is a natural polyphenol compound of yellow pigment, derived from the rhizome of the Curcuma longa plant. According to previous studies found that the pharmacological activity of curcumin is not stable in vivo. Furthermore,it is difficulty absorbed through the gastrointestinal tract. Acting on the blood concentration is not high thus may result in limited its efficacy. Recently, previous studies showed that tetrahydrocurcumin has similar same physiological and pharmacological properties as the active form of curcumin in vivo and it’s more stable than curcumin. Tetrahydrocurcumin has been widely studied due to its potential antioxidant, anti-inflammatory, and anticarcinogenic activities as well as hepatoprotective. However, the mechanism of action and how it causes hepatocellular carcinoma cell death still no literature shows.
The present studies demonstrate that Tetrahydrocurcumin significantly inhibits hepatocellular carcinoma cell proliferation.When hepatocellular carcinoma cell were treated with Tetrahydrocurcumin under the specific concentration,it neither displays features typical apoptosis nor cell cycle arrest to inhibit cancer cell growth.So we based on the characteristics of autophagy,our studies demonstrate that Tetrahydrocurcumin significantly promote autophage marker acidic vascular organelles and EGFP-LC3 punctas formation. At the molecular levels, the results showed that Tetrahydrocurcumin significantly increased autophagy-related protein expression.In addition,Tetrahydrocurcumin may induced autophagic cell death through modulation of PI3K/Akt-mTOR signal transduction pathyway in human hepatocellular carcinoma cells.Then we further suppressed tetrahydrocurcumin -induced autophagy process by autophagy inhibitors.The results showed that autophagy inhibitor didn’t make hepatocellular carcinoma cells revive.On the contrary,it accelerated tetrahydrocurcumin choose to switch another way of apoptosis.
In clinical,Doxorubicin has been commonly used as a chemotherapeutic drug in the treatment of hepatocellular carcinoma patients.But it tend to cause some adverse effects and drug resistance for patients ,this is still thorny problem so far. Accordingly, we aim to investigate the effects of tetrahydrocurcumin combined with doxorubicin for treatment strategy. The results from Isobologram assay and drugs combination index analysis showed that the effects is belong to the synergy in hepatocellular carcinoma cells between the two drugs.We found that the combined effect of drugs effectively enhanced apoptosis in HepG2 cells.
Taken toghter, our present studies demonstrated tetrahydrocurcumin could induce autophagy to inhibit the growth of human hepatocellular carcinoma cells in vitro.And we also have shown for the first time that tetrahydrocurcumin could augment antitumor activity of doxorubicin in vivo.But the mechanism of tetrahydrocurcumin still needs further discussion and evaluation in hepatocellular carcinoma.For future,we provided a choice of targeted drugs and adjuvant drugs for clinical treatment.This is a reference value and has a potential application for hepatocellular carcinoma.
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