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

Abstract

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.

Interferon-omega: Current status in clinical applications

“…Similarly, injecting the gene encoding interferon ω1 via the tail vein into mice bearing a Hep-A-22 liver tumor via liposomal gene delivery also significantly decreased tumor weights [53]. Interestingly, this effect was greater (43% tumor inhibition) only when the plasmid contained human thymosin alpha 1 [53]. A DNA ladder (a hallmark of cells undergoing apoptosis) was observed in the tumor cells treated by IFN-ω.…”

“…This kind of effect was due to the induction of reactive oxygen species generation, mitochondrial membrane potential disruption, and calcium uptake, indicating that fFeIFN-ω lipofection is an alternative approach for treating both sensitive and resistant phenotypes with an equal or superior outcome and with fewer adverse effects than recombinant fFeIFN-ω therapy [52]. Similarly, injecting the gene encoding interferon ω1 via the tail vein into mice bearing a Hep-A-22 liver tumor via liposomal gene delivery also significantly decreased tumor weights [53]. Interestingly, this effect was greater (43% tumor inhibition) only when the plasmid contained human thymosin alpha 1 [53].…”

“…A DNA ladder (a hallmark of cells undergoing apoptosis) was observed in the tumor cells treated by IFN-ω. Interestingly, the antitumor mechanisms involve increasing the expression of Tα1 and IFN-ω, and a plasmid-liposome complex of IFN-ω and IFN-α together exerted greater potency in inhibiting the growth of Hep-A-22 tumor cells than either compound alone [53].…”

Cloning, Prokaryotic Soluble Expression, and Analysis of Antiviral Activity of Two Novel Feline IFN-ω Proteins

“…Recently, combination antiviral therapy has become a common practice in treating feline viral infections due to pharmacokinetics and the short half-life of IFN alone [48,49]. There are many published studies focused on the combination of IFN-ω with other therapeutic agents, such as chemotherapeutic agents [50], IFN-α [51], and ribavirin [6], suggesting this is an attractive strategy to use against viral infections. We further evaluated the antiviral effects of rfeIFN-ωa and rfeIFN-ωb combined with feline IL-18 against VSV and FCoV in F81 cells.…”

Thymosin alpha 1: Biological activities, applications and genetic engineering production

“…T␣1 in combination with other BRMs or chemotherapy agents also displays good effects in reducing tumor burden and progression. The plasmid-liposome complex containing the cDNA of human T␣1 and IFN 1 was injected into ICR mice, and the dual-gene plasmid-liposome complex showed stronger inhibitory effect on the growth of tumor than the single gene of T␣1 or IFN 1, which might attribute to indirect and additive induction of apoptosis of tumor cells by the increased expression of T␣1 and IFN 1 [12]. In DHD-K12 colorectal cancer model, combination of 5-FU, IL-2 and T␣1 could dramatically increase survival rates as well as control tumor metastasis [26].…”