Effect Of Iodized Poppy Seed Oil On Hepatocellular Carcinoma Cells And Solid Tumor

Liver cancer is one of the leading causes of cancer-related death,second only to lung and stomach cancer.Liver cancer is a highly fatal tumor,most cases are found in advanced stages,and the ratio of morbidity to mortality is close to 1.Due to the varying prevalence of potential risk factors,the incidence of HCC is heterogeneous worldwide.Hepatocellular carcinoma(HCC)has the highest incidence in east Asia and Africa,with an estimated 72%of cases occurring in Asia(with over 50%in China),10%in Africa,10%in Latin America,7.8%in Europe,5.1%in North America and 4.6%in Oceania.Morbidity and mortality rates are rising rapidly in the United States and Europe.In traditionally high-risk regions,such as parts of Asia such as China and Japan,liver cancer incidence and death rates are falling,but the overall base is still high.Hepatocellular carcinoma(HCC)accounts for approximately 75%and 85%of primary liver cancer and is a major health problem worldwide.The major contributors to hepatocellular carcinoma are chronic hepatitis c.virus(HCV)or hepatitis b virus(HBV),heavy drinking,aflatoxin,diabetes,obesity,and non-alcoholic fatty liver disease(NAFLD).Treatment in patients with hepatocellular carcinoma depends on the stage of the tumor.Hepatectomy remains the preferred treatment for early hepatocellular carcinoma(HCC),and liver transplantation is effective for early HCC that meets the milan criteria.However,the clinical symptoms of early hepatocellular carcinoma are mild and easy to be ignored by patients.Therefore,diagnosed patients are generally in the middle and late stage of hepatocytes,and hepatectomy cannot effectively improve the prognosis and survival rate of patients.With advances in surgical techniques and instruments and the development of molecular-targeted drugs,some potential therapies have become possible.Most patients in the middle and late stages receive palliative or symptomatic treatment,such as radiofrequency ablation,interventional therapy for liver cancer(transcatheter arterial chemoembolization),radioembolization,and immunotherapy.The staging of hepatocellular carcinoma is important to evaluate the resectability of the tumor,to choose the appropriate treatment and to predict the prognosis of the patient.The liver gets 25%of its blood supply from the hepatic arteries and 75%from the portal vein,while 90%of the blood supply in HCC comes from the hepatic arteries and only 10%from the portal vein.This difference provides a theoretical basis for blocking the blood supply of hepatocellular carcinoma through local chemotherapy and inducing tumor necrosis without significantly affecting the blood supply to the liver.Transcatheter chemoembolization is mainly used in patients with hepatocellular carcinoma of Barcelona stage B(BCLC-B).Iodized poppy seed oil is mixed with chemotherapeutic drugs to form an emulsion and combine with Absorbable Gelatin Sponge to achieve the effect of embolization,resulting in tumor necrosis.It has been found that iodized poppy seed oil mainly exists in tumor tissues in the liver,which may be caused by abnormal tumor vascular or lymphatic drainage.The mechanism of this deposition remains unclear.In vitro,we found that the mixture of chemotherapy drugs and iodized poppy seed oil was only temporary,so this study will explore the direct effect of iodized poppy seed oil on huh-7 cells and liver solid tumors.The morphological changes of huh-7 cells were observed by scanning electron microscopy(SEM)and transmission electron microscopy(TEM).Cell viability was determined by trypan blue staining.Changes in mitochondrial transmembrane potential,reactive oxygen species(ROS)and adenosine triphosphate(ATP)were detected.The distribution of iodized oil in mouse solid tumors was evaluated by CT imaging,oil red O staining,hematoxylin and eosin(H&E)staining.Cytoskeletal gene expression was detected by qPCR.We found that after direct interaction with iodide oil,tumor cell volume gradually decreased and microvilli gradually disappeared with time.TEM confirmed intracellular mitochondrial swelling and iodide oil entry.Cell membrane integrity was impaired,and cell necrosis reached 97%at 4h.After the interaction between iodide oil and huh-7 cells,mitochondrial ATP synthesis decreased,ROS accumulation,and membrane potential decreased.After iodide oil was injected directly into solid tumor,CT imaging showed that iodide oil was fully deposited in the tumor,bright red oil droplets were observed in both intracellular and intercellular Spaces,and tumor necrosis was observed by H&E staining.The expression of cytoskeletal genes decreased with the prolongation of cell contact time with iodized oil.It can be seen that iodized poppy seed oil,when directly acting on huh7 cells and liver solid tumors,will cause cell contraction and contraction,induce mitochondrial dysfunction and ROS accumulation,destroy the cytoskeleton,destroy the integrity of the cell membrane,and enter cells,leading to tumor cell necrosis.