Liver Tumor Growth Research Articles

Mathematical modeling of liver metastases tumour growth and control with radiotherapy

Generating an optimized radiation treatment plan requires understanding the factors affecting tumour control. Mathematical models of tumour dynamics may help in future studies of factors predicting tumour sensitivity to radiotherapy. In this study, a time-dependent differential model, incorporating biological cancer markers, is presented to describe pre-treatment tumour growth, response to radiation, and recurrence. The model uses Gompertzian-Exponential growth to model pre-treatment tumour growth. The effect of radiotherapy is handled by a realistic cell-kill term that includes a volume-dependent change in tumour sensitivity. Post-treatment, a Gompertzian, accelerated, delayed repopulation is employed. As proof of concept, we examined the fit of the model's prediction using various liver enzyme levels as markers of metastatic liver tumour growth in a liver cancer patient. A tumour clonogen population model was formulated. Each enzyme was coupled to the same tumour population, and served as surrogates of the tumour. This dynamical model was solved numerically and compared to the measured enzyme levels. By minimizing the mean-squared error of the model enzyme predictions, we determined the following tumour model parameters: growth rate prior to treatment was 0.52% per day; the fractional radiation cell kill for the prescribed dose (60 Gy in 15 fractions) was 42% per day, and the tumour repopulation rate was 2.9% per day. These preliminary results provided the basis to test the model in a larger series of patients, to apply biological markers for improving the efficacy of radiotherapy by determining the underlying tumour dynamics.

Nitric Oxide Regulates Tumor Cell Cross-Talk with Stromal Cells in the Tumor Microenvironment of the Liver

Tumor progression is regulated through paracrine interactions between tumor cells and stromal cells in the microenvironment, including endothelial cells and myofibroblasts. Nitric oxide (NO) is a key molecule in the regulation of tumor-microenvironment interactions, although its precise role is incompletely defined. By using complementary in vitro and in vivo approaches, we studied the effect of endothelial NO synthase (eNOS)-derived NO on liver tumor growth and metastasis in relation to adjacent stromal myofibroblasts and matrix because liver tumors maintain a rich, vascular stromal network enriched with phenotypically heterogeneous myofibroblasts. Mice with an eNOS deficiency developed liver tumors more frequently in response to carcinogens compared with control animals. In a surgical model of pancreatic cancer liver metastasis, eNOS overexpression in the tumor microenvironment attenuated both the number and size of tumor implants. NO promoted anoikis of tumor cells in vitro and limited their invasive capacity. Because tumor cell anoikis and invasion are both regulated by myofibroblast-derived matrix, we explored the effect of NO on tumor cell protease expression. Both microarray and Western blot analysis revealed eNOS-dependent down-regulation of the matrix protease cathepsin B within tumor cells, and silencing of cathepsin B attenuated tumor cell invasive capacity in a similar manner to that observed with eNOS overexpression. Thus, a NO gradient within the tumor microenvironment influences tumor progression through orchestrated molecular interactions between tumor cells and stroma.

Sometimes Less Is More: Perinatal Bacterial Exposure May Be More Important than Hepatitis for Liver Tumor Development

Vol. 116, No. 10 EnvironewsOpen AccessSometimes Less Is More: Perinatal Bacterial Exposure May Be More Important than Hepatitis for Liver Tumor Development David A. Taylor David A. Taylor Search for more papers by this author Published:1 October 2008https://doi.org/10.1289/ehp.116-a440bAboutSectionsPDF ToolsDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InRedditEmail Helicobacter hepaticus, a bacterium discovered in 1994 and widespread in many experimental mouse populations, is associated with a high incidence of liver tumors in aging mice. A new mouse study shows that perinatal exposure to this pathogen, rather than development of hepatitis itself, may be the single most important factor in the development of liver tumors caused by H. hepaticus[EHP 116:1352–1356; Diwan et al.]. The results support evidence from other studies that progressive hepatitis and liver tumors in older mice may stem from early-life exposure.The researchers isolated a strain of H. hepaticus from infected A/J mice. Female mice received injections with a single dose of the bacteria. Females testing positive for the bacteria were bred with uninfected males. The researchers assessed liver histopathologic findings and tumor growth in male offspring aged 2 weeks to 2 years. Uninfected weanling males from another lab were injected at 3–4 weeks.The results showed a significant incidence of liver tumors in the offspring after intraperitoneal maternal exposure to the bacteria: 33% developed liver tumors, usually multiple tumors, and 18% developed hepatocellular carcinoma. None of the mice injected with the bacteria as young adults developed any tumors.Another striking result was that tumor outcome was not closely linked to severity of hepatitis; mice that contracted hepatitis did not necessarily develop hepatic tumors. Rather, it appeared that early exposure to the bacteria, not the hepatitis itself, was key to fostering tumor growth.The type of additional perinatal event required to induce tumor development is unknown but could involve DNA damage at that vulnerable early stage, followed by subacute inflammation of the liver in response to H. hepaticus infection. The authors note that similar scenarios could apply to human infection with Helicobacter pylori and other pathogens linked with cancer. The results point to the need for further study of changes in perinatal tissues in response to such infections.FiguresReferencesRelatedDetails Vol. 116, No. 10 October 2008Metrics About Article Metrics Publication History Originally published1 October 2008Published in print1 October 2008 Financial disclosures License information EHP is an open-access journal published with support from the National Institute of Environmental Health Sciences, National Institutes of Health. All content is public domain unless otherwise noted. Note to readers with disabilities EHP strives to ensure that all journal content is accessible to all readers. However, some figures and Supplemental Material published in EHP articles may not conform to 508 standards due to the complexity of the information being presented. If you need assistance accessing journal content, please contact [email protected]. Our staff will work with you to assess and meet your accessibility needs within 3 working days.

Poster - Thurs Eve-04: Mathematical modeling of liver metastases tumour growth and control with radiotherapy.

Generating an optimized radiation treatment plan requires understanding the factors affecting tumour control. Mathematical models of tumour dynamics may help in future studies of factors predicting tumor sensitivity to radiotherapy. In this study, a time-dependent differential model, incorporating biological cancer markers, is presented to describe pre-treatment tumour growth, response to radiation, and recurrence. The model uses Gompertzian growth to model pre-treatment tumour growth. The effect of radiotherapy is handled by a realistic cell-kill term that includes a volume-dependent change in tumour sensitivity. Post-treatment, a Gompertzian, accelerated, delayed repopulation is employed. As proof-of-concept, we examined the fit of the model's prediction using various liver enzyme levels as markers of metastatic liver tumour growth in a liver cancer patient. Enzyme data were derived from repeated serum blood tests, and radiation treatment-related data were retrieved from the patient's chart. A tumour clonogen population model was formulated. Each enzyme was coupled to the same tumour population, and served as surrogates of the tumour. This dynamical model was solved numerically and compared to the measured enzyme levels. By minimizing the mean-squared error of the model enzyme predictions, we determined the following tumour model parameters: growth rate prior to treatment was 0.7% per day; the fractional radiation cell kill for the prescribed dose was 60% per day; and tumour repopulation rate was 3.5% per day. These preliminary results provided the basis to test the model in a larger series of patients, to apply biological markers for improving the efficacy of radiotherapy by determining the underlying tumour dynamics.

RNAi-mediated ERK2 knockdown inhibits growth of tumor cells in vitro and in vivo

The MAPK MEK/ERK pathway is often upregulated in cancer cells and represents an attractive target for development of anticancer drugs. Only few data concerning the specific functions of ERK1 and 2 are reported in the literature. In this report, we investigated the specific role of ERK1 and 2 in liver tumor growth both in vitro and in vivo. DNA synthesis and cells in S phase analysed by flow cytometry, correlated with strong inhibition of Cdk1 and cyclin E levels, are strongly reduced after exposure to the MEK inhibitor, U0126. We obtained a significant reduction of colony formation in soft agar assays and a reduction in the size of tumor xenografts in nude mice treated with U0126. Then, we could specifically abolished ERK1 or 2 expression by small-interfering RNA (siRNA) and demonstrated that ERK2 knockdown but not ERK1 interferes with the process of replication. Moreover, we found that colony formation and tumor growth in vivo were significantly inhibited by targeting ERK2 using stable chemically modified siRNA. Taken together, our results emphasize the importance of the MEK/ERK pathway in liver cancer cell growth in vitro and in vivo and argue for a crucial role of ERK2 in this regulation.

Geranylgeraniol suppresses the proliferation of murine melanoma cells and human prostate tumor cells

The rate‐limiting activity of the mevalonate pathway, 3‐hydroxy‐3‐methylglutaryl coenzyme A (HMG CoA) reductase, provides essential intermediates for the prenylation or dolichylation of growth‐related proteins including nuclear lamins, Ras and growth factor receptors. A diterpene geranylgeraniol accelerates HMG CoA reductase degradation and suppresses the growth of human liver, lung, ovary, pancreas, colon, stomach, and blood tumors. We evaluated geranylgeraniol in murine and human cells. Geranylgeraniol induced dose‐dependent suppression of the cell proliferation following 48 (murine B16 melanoma) or 72 (human DU145 prostate carcinoma) h incubations in 96‐well plates. Cell cycle arrest at the G1 phase, manifested by a dose‐dependent increase in G1/S ratio, and apoptosis detected by fluorescence microscopy following acridine orange and ethidium bromide dual staining, contribute to the growth suppression in DU145 cells. The impact of geranylgeraniol on B16 cell proliferation was attenuated by supplemental mevalonate. Geranylgeraniol also attenuated the growth of human LNCaP prostate carcinoma and PC‐3 prostate adenocarcinoma cells. Mouse 3T3‐L1 fibroblasts were more resistant than B16 cells to geranylgeraniol. The differential sensitivity between neoplastic and normal cells points to the potential application of geranylgeraniol to cancer prevention. TDA, TWU REP & Summer Stipend Award.

Small interfering RNA targeting CDC25B inhibits liver tumor growth in vitro and in vivo

BackgroundUsing gene expression profiling, we previously identified CDC25B to be significantly highly expressed in hepatocellular carcinoma (HCC) compared to non-tumor liver. CDC25B is a cell cycle-activating phosphatase that positively regulates the activity of cyclin-dependent kinases, and is over-expressed in a variety of human malignancies. In this study, we validated the over-expression of CDC25B in HCC, and further investigated its potential as a therapeutic target for the management of HCC.ResultsQuantitative real-time polymerase chain reaction and immunohistochemical staining of patient samples confirmed the significant over-expression of CDC25B in HCC compared to non-tumor liver samples (P < 0.001). Thus, intefering with the expression and activity of CDC25B may be a potential way to intervene with HCC progression. We used RNA interference to study the biological effects of silencing CDC25B expression in HCC cell lines (Hep3B and Hep40), in order to validate its potential as a therapeutic target. Using small oligo siRNAs targeting the coding region of CDC25B, we effectively suppressed CDC25B expression by up to 90%. This was associatetd with significant reductions in cell growth rate, cell migration and invasion through the matrigel membrane, and caused significant cell cycle delay at the G2 phase. Finally, suppression of CDC25B significantly slowed the growth of Hep40 xenografts in nude mice.ConclusionOur data provide evidence that the inhibition of CDC25B expression and activity lead to suppression of tumor cell growth and motility, and may therefore be a feasible approach in the clinical management of HCC.

SOCS3 in Liver Regeneration and Hepatocarcinoma

Cytokine responses are stringently controlled by a family of proteinsSTAT3 termed the suppressors of cytokine signaling (SOCS), and deregulation of SOCS function is associated with many diseases, including several cancers, disorders in hematopoiesis, and autoimmune diseases. Our current understanding of the divergent roles of SOCS3 has recently improved and indicates that SOCS3 is critical in modulating cytokine-mediated and neoplastic-proliferative responses in the liver. The generation of hepatocyte-specific Socs3 knockout mice suggests that loss of SOCS3 expression encourages hepatocyte proliferation, survival, and hepatocellular carcinoma formation. By elucidating the regulation of pathways leading to liver regeneration we may gain useful insights to control liver disease and tumor growth.

Abstract No. 160: Technical Considerations for Reliable Vx-2 Liver Tumor Growth: Selection of Implantation Site

Abstract No. 160: Technical Considerations for Reliable Vx-2 Liver Tumor Growth: Selection of Implantation Site

Abstract No. 369: Technical Considerations for Reliable Vx-2 Liver Tumor Growth: Selection of Tumor Cells Inoculation Method

Abstract No. 369: Technical Considerations for Reliable Vx-2 Liver Tumor Growth: Selection of Tumor Cells Inoculation Method

Acceleration of primary liver tumor growth rate in embolized hepatic lobe after portal vein embolization

Portal vein embolization (PVE) is now widely accepted as a useful preoperative procedure in selected patients undergoing extended hepatectomy. However, the effect of PVE on the growth of liver tumors has not been fully elucidated. To retrospectively evaluate the effects of PVE on the growth of liver tumors in the embolized lobes. Eight patients with a primary liver tumor, six hepatocellular carcinomas (HCC) and two cholangiocellular carcinomas (CCC), were studied. The growth rates of the tumors in the embolized lobes and non-embolized liver parenchyma were calculated using the computed tomography (CT) volume values at the time of tumor identification, and before and after PVE. The median tumor growth rate was 0.59 cm(3)/day (range 0.22-6.01 cm(3)/day) before PVE and 2.37 cm(3)/day (range 0.29-13.97 cm(3)/day) after PVE (P = 0.018). The tumor growth acceleration ratios ranged from 1.50 to 7.46 (median 2.65) in the six HCCs, and were 1.00 and 1.32 in the two CCCs. There was no apparent correlation between the tumor growth rate after PVE and the growth rate of non-embolized liver parenchyma (median 6.00 cm(3)/day, range 1.24-11.0 cm(3)/day). Liver tumor growth in an embolized lobe accelerates after PVE, in patients with HCC.

The Effect of Meloxicam, a Selective COX-2 Inhibitor, on the Microvasculature of Small Metastatic Liver Tumors in Rats

COX-2 is involved in tumor angiogenesis and modulation of the production of angiogenetic factors by colorectal carcinoma cells. It has been shown that COX-2 inhibitors have inhibitory activities against various types of tumor, including colorectal carcinoma. In this study, we investigated the tumor vessels of small metastatic liver tumors in rats and the effect of meloxicam, a selective COX-2 inhibitor, on their growth and microvasculature. The metastatic liver tumors were produced by intraportal inoculation of RCN-H4 cells in male F344/DuCrj rats (n = 40). The microvasculature was examined by scanning electron microscopy and stereomicroscopy. Microvascular casts were produced by perfusion via the abdominal aorta 14 days after tumor inoculation. Four groups (control, groups 1-3) of rats were treated with meloxicam 0, 0.6, 1.0 and 3.0 mg/kg/day, respectively, by oral gavage 5 days/week for two weeks from the day of inoculation of RCN-H4 cells. The mean number of tumors was significantly decreased in groups 1-3 (5.6+/-0.8 standard deviation, SD; 3.6+/-1.1; and 5.5+/-1.1, respectively) compared with control (11.2+/-2.7; P = 0.0002, each). Meloxicam also significantly reduced the mean diameter of the tumor: 730+/-254, 685+/-212 and 644+/-139 in groups 1-3, respectively, in comparison with 870+/-276 in control (P = 0.0025, 0.0011 and <0.0001, respectively). Meloxicam's anti-angiogenic activity interferes with the growth of metastatic liver tumors. Meloxicam might have therapeutic potential for liver metastasis of colorectal carcinoma.

Liver embolizations in oncology: A review

Arterial embolization of the liver often temporarily retards the growth of liver tumors which are mainly nourished arterially. The use of degradable agents avoids collateral formation which would prohibit repeat procedures and permit tumor regrowth. The effect of embolizations is largest in small hypervascular lesions, e.g., many hepatocellular or neuroendocrine cancers. Toxic chemicals can be added, chemoembolization, with unproven effects on responses and survival rates. Institutional differences in indications and procedures make evaluation of embolizations difficult. However, intermediate-term survival increases in selected cases of unresectable hepatocellular cancers and hormonal symptoms from neuroendocrine tumors often improve. Scant experience supports embolization for anti-tumoral effects in some pediatric tumors, to control bleeding from ruptured tumors, for symptomatic hemangiomas, and for downstaging of hepatocellular cancers before transplantation.

Histamine and spontaneously released mast cell granules affect the cell growth of human hepatocellular carcinoma cells

The role of mast cells in tumor growth is still controversial. In this study we analyzed the effects of both histamine and pre-formed mediators spontaneously released by mast cells on the growth of two human hepatocellular carcinoma cell lines, HA22T/VGH and HuH-6, with different characteristics of differentiation, biological behavior and genetic defects. We showed that total mast cell releasate, exocytosed granules (granule remnants) and histamine reduced cell viability and proliferation in HuH-6 cells. In contrast, in HA22T/VGH cells granule remnants and histamine induced a weak but significant increase in cell growth. We showed that both cell lines expressed histamine receptors H(1) and H(2) and that the selective H(1) antagonist terfenadine reverted the histamine-induced inhibition of HuH-6 cell growth, whereas the selective H(2) antagonist ranitidine inhibited the histamine-induced cell growth of HA22T/VGH cells. We demonstrated that histamine down-regulated the expression of beta-catenin, COX-2 and survivin in HuH-6 cells and that this was associated with caspase-3 activation and PARP cleavage. On the contrary, in HA22T/VGH cells expression of survivin and beta-catenin increased after treatment with granule remnants and histamine. Overall, our results suggest that mediators stored in mast cell granules and histamine may affect the growth of liver cancer cells. However, mast cells and histamine may play different roles depending on the tumor cell features. Finally, these data suggest that histamine and histamine receptor agonists/antagonists might be considered as "new therapeutic" drugs to inhibit liver tumor growth.

Hepatic Resection but Not Radiofrequency Ablation Results in Tumor Growth and Increased Growth Factor Expression

The purpose of this study was to examine the effects of radiofrequency ablation (RFA) on tumor growth and growth factor expression in a murine model. Surgical excision remains the only potentially curative therapy for hepatic malignancies. Tumor growth in the remaining liver may be accelerated after resection. The mechanism of this enhanced tumor growth remains unexplained, although growth factors that are released after hepatic resection (which facilitate liver regeneration) may play a role in residual tumor growth. RFA has become a viable alternative for patients who are not candidates for a curative resection. The effect of RFA on tumor growth and growth factor expression has not been studied. Hepatic tumors were established by direct injection with CT-26, a murine adenocarcinoma. Tumors were treated by either partial hepatic resection (PH) or RFA. Hepatocyte growth factor (HGF) and basic fibroblast growth factor (bFGF) expression was measured at selected time intervals post-treatment. Tumor growth was measured by reinjection of CT-26 into the residual liver after treatment. Nine days after reinjection, tumor volume was calculated and compared with nontreated controls. HGF and bFGF expression was significantly higher at baseline in the CT-26 tumor-bearing mice when compared with non-tumor-bearing controls (P = 0.00001 and P = 9 x 10, respectively). There was an increase in HGF and bFGF expression at 24 hours (P = 0.005, and P = 0.001) in the PH group. In the RFA group, there was a decrease in HGF and bFGF expression at 24 and 72 hours (P = 0.001 and P = 0.002). Tumor growth comparisons revealed an increase in tumor growth in the hepatectomy group (P = 0.006) but not the RFA group (P = 0.2). Baseline growth factor expression in tumor-bearing mice is exponentially higher when compared with non-tumor-bearing controls. HGF and bFGF expression are increased posthepatectomy, and decreased post-RFA. Partial hepatectomy results in an increase in tumor growth in the residual liver. RFA did not increase tumor growth after treatment. While hepatectomy is the only curative option for patients with hepatic malignancies, it may accelerate growth of microscopic residual disease.

Combined GM-CSF and IL-12 gene therapy synergistically suppresses the growth of orthotopic liver tumors

Immunotherapy is often effective only for small tumor burdens and, in many cases, is restricted to subcutaneous tumors. Here, we investigated the antitumor effects of combination therapy with GM-CSF and IL-12 on orthotopic liver tumors with intermediate or large tumor volumes, or on chemically-induced multifocal liver tumors in animals. Adenoviruses encoding GM-CSF or IL-12 were injected intratumorally to animals bearing transplanted tumors, or injected via intrahepatic artery in animals with primary multifocal liver tumors induced by diethylnitrosamine. Our results demonstrated that IL-12, but not GM-CSF, monotherapy displayed significant therapeutic effects, whereas combination therapy with both cytokines displayed synergistic antitumor effects not only on transplanted tumor models with intermediate or large tumor loads, but also on carcinogen-induced multifocal liver tumors. Effector cell analyses, revealed by in vivo cell subset depletion, flow cytometry analysis, and immunohistochemical staining of tumor infiltrates, indicated that NK cells were the prominent antitumor effectors for the IL-12-mediated antitumor activity, whereas CD8+ T cells, NKT cells, and macrophages were more important than NK cells in the combination therapy-mediated antitumor effects. Both IL-12 monotherapy and combination therapy could induce various types of effectors and high levels of IFN-gamma; however, the latter induced much higher levels than the former, which may explain why combination therapy is superior to IL-12 monotherapy. Combination therapy with GM-CSF and IL-12 represents a promising immunotherapy strategy for treating orthotopic, widespread liver tumors.

Ischemia-reperfusion of small liver remnant promotes liver tumor growth and metastases—Activation of cell invasion and migration pathways

Elucidating the mechanism of liver tumor growth and metastasis after hepatic ischemia-reperfusion (I/R) injury of a small liver remnant will lay the foundation for the development of therapeutic strategies to target small liver remnant injury, and will reduce the likelihood of tumor recurrence after major hepatectomy or liver transplantation for liver cancer patients. In the current study, we aimed to investigate the effect of hepatic I/R injury of a small liver remnant on liver tumor development and metastases, and to explore the precise molecular mechanisms. A rat liver tumor model that underwent partial hepatic I/R injury with or without major hepatectomy was investigated. Liver tumor growth and metastases were compared among the groups with different surgical stress. An orthotopic liver tumor nude mice model was used to further confirm the invasiveness of the tumor cells from the above rat liver tumor model. Significant tumor growth and intrahepatic metastasis (5 of 6 vs. 0 of 6, P=0.015), and lung metastasis (5 of 6 vs. 0 of 6, P=0.015) were found in rats undergoing I/R and major hepatectomy compared with the control group, and was accompanied by upregulation of mRNA levels for Cdc42, ROCK (Rho kinase), and vascular endothelial growth factor, as well as activation of hepatic stellate cells. Most of the nude mice implanted with liver tumor from rats under I/R injury and major hepatectomy developed intrahepatic and lung metastases. In conclusion, hepatic I/R injury of a small liver remnant exacerbated liver tumor growth and metastasis by marked activation of cell adhesion, invasion, and angiogenesis pathways.

157 POSTER Combination therapy for liver tumor growth and metastasis by low dose rapamycin and FTY720

We studied the effect of annealing conditions on magnetic properties of amorphous CoFeNi-based glass-coated microwires. We showed that annealing can be very effective for manipulation of the magnetic properties of amorphous ferromagnetic glass-coated microwires. Low coercivity and high Gaint magnetoimpedance (GMI) effect have been observed in as-prepared Co-rich microwires. After annealing of Co-rich we can observe transformation of linear hysteresis loops to rectangular and coexistence of fast magnetization switching and GMI effect in the same sample. We demonstrated that the coercivity of microwires can be tailored by annealing in the range from 4 to 200 A/m. We found that the annealing considerably affects the magnetostriction coefficient and observed correlation between the magnetic hardening of studied microwires and the magnetostriction sign change.

A new expression plasmid in Bifidobacterium longum as a delivery system of endostatin for cancer gene therapy

To utilize Bifidobacterium longum (B. longum) as a safe and stable delivery system for endostatin in cancer gene therapy, we constructed pBV22210 vector combining a chloramphenicol-resistance gene (Cm(r)) from pBCSK(+) plasmid, a cryptic plasmid pMB1 from B. longum strain with pBV222. Endostatin was cloned directly downstream of an N terminal His6-tag sequence in the pBV22210, so that the endostatin protein expressed in B. longum could be purified with Ni-binding resin. The results indicated that the plasmid electroporated into B. longum was maintained stably in the absence of selective antibiotics and did not significantly affect biological characteristics of B. longum. In addition, the plasmid in B. longum showed a strong inhibitory effect on the growth of mouse solid liver tumor in vivo. These results suggested that this new plasmid may be a stable vector in B. longum for transporting anti-cancer genes in cancer gene therapy.

Liposomal plasmid DNA encoding human thymosin α1 and interferon ω1 potently inhibits liver tumor growth in ICR mice

To evaluate the potential therapeutic effect of liposomal gene delivery, genes encoding for human thymosin alpha1 (Talpha1) and interferon omega1 were injected via the tail vein into mice bearing a Hep-A-22 liver tumor. The cDNA of human Talpha1 and interferon omega1 were obtained by synthesis or reverse transcription-polymerase chain reaction (RT-PCR), respectively. Eukaryotic expressing vectors pIRES2, encoding Talpha1 and/or interferon omega1, were constructed and injected with liposome via the tail vein into ICR mice bearing a Hep-A-22 tumor. The potency of tumor inhibition was evaluated when three treated groups were compared with the group receiving the empty vector. Apoptosis of tumor cells was investigated by analyzing DNA fragmentation. Only the group treated with dual-gene plasmid reached an eligible level of tumor inhibition (43%). The difference in tumor weight was statistically significant between the Talpha1 gene or the interferon omega1 gene treated groups and the control (P<0.05), and highly significant between the dual-gene treated group and the control (P<0.01). DNA ladder was observed in the tumor cells from the purpose gene treated groups but not from the control. The dual-gene plasmid-liposome complex showed more potent inhibition than the single gene constructs on the growth of Hep-A-22 tumor cells in mice, which may be attributed to indirect and additive induction of apoptosis in tumor cells by increased expression of Talpha1 and interferon omega1.