8 kinesiska forskare har fått sina studier om en cancer med dåliga överlevnadschanser granskade,godkända och publicerade.Det handlar om levercancer (hepatocellular carcinoma) som skördar 800 000 människoliv om året.Denna cancertyp är riktigt lömsk då den oftast inte upptäcks förrän det är försent att sätta in räddande behandling.Man opererar om så går och tar då bort tumören eller i värsta fall hela levern.Det brukar resultera i behov av en levertransplantation.Har cancern gått för långt kan man inte operera utan ger patienten läkemedel som dessväre inte visat sig ha nån större effekt.
Överlevnad vid denna behandlingsform sträcker sig ca 3 månader från diagnos.
Behovet att ett helt nytt läkemedel är mao stort och det är med den målsättningen dessa forskare har bedrivit sina studier.Intressant är att de gått tillbaka till kinesisk urminnesmedicin,dvs extract från örter osv..Här har de använt sig av en substans från roten ginseng,20(S)-protopanaxadiol (20(S)-PPD) och fått fram lovande resultat.
Forskarna har behövt använda sig av PHI`s HoloMonitor för att kunna studera cancerceller behandlade med substansen.Det inne i en inkubator under 24 timmar med 30 minuters intervaller.
Received 1 April 2021, Revised 25 May 2021, Accepted 1 June 2021, Available online 10 June 2021.
Abstract
Background
20(S)-protopanaxadiol (20(S)-PPD), one of the main active metabolites
of ginseng, performs a broad spectrum of anti-tumor effects. Our aims
are to search out new strategies to enhance anti-tumor effects of
natural products, including 20(S)-PPD. In recent years, fasting has been
shown to be multi-functional on tumor progression. Here, the effects of
fasting combined with 20(S)-PPD on hepatocellular carcinoma growth, apoptosis, migration, invasion and cell cycle were explored.
Methods
CCK-8
assay, trypan blue dye exclusion test, imagings photographed by
HoloMonitorTM M4, transwell assay and flow cytometry assay were
performed for functional analyses on cell proliferation,
morphology, migration, invasion, apoptosis, necrosis and cell cycle.
The expressions of genes on protein levels were tested by western blot.
Tumor-bearing mice were used to evaluate the effects of intermittent fasting combined with 20(S)-PPD.
Results
We firstly confirmed that fasting-mimicking increased the anti-proliferation effect of 20(S)-PPD in human HepG2 cells in vitro.
In fasting-mimicking culturing medium, the apoptosis and necrosis
induced by 20(S)-PPD increased and more cells were arrested at G0-G1
phase. Meanwhile, invasion and migration of cells were decreased by
down-regulating the expressions of matrix metalloproteinase (MMP)-2 and
MMP-9 in fasting-mimicking medium. Furthermore, the in vivo
study confirmed that intermittent fasting enhanced the tumor growth
inhibition of 20(S)-PPD in H22 tumor-bearing mice without obvious side
effects.
Conclusion
Fasting significantly sensitized HCC cells to 20(S)-PPD in vivo and in vitro. These data indicated that dietary restriction can be one of the potential strategies of chinese medicine or its active metabolites against hepatocellular carcinoma.
Materials and Methods (urval)
2.7. HoloMonitorTM M4 analysis
The
HoloMonitorTM M4 (Phase Holographic Imaging, Lund, Sweden), placed in a
standard cell culture incubator, was used to record proliferation,
track and related parameters of HepG2 cells which were exposured to
20(S)-PPD in control medium or fasting-mimicking medium in 6-well
plates. Imaging was conducted every 30 mins for 24 h and analyzed by
HoloMonitor software.
(D) The cell morphology
analyzed by HoloMonitorTM M4 and real-time holographic imaging were
recorded at the doses indicated (24 h). Differences were considered as
significant when P < 0.05 (∗) or P < 0.01 (∗∗) or P < 0.001 (∗∗∗).
3D reconstruction imaging (Fig. 4)
has an advantage for the comparison of cell volumn and morphology
(i.e., thickness). Acquisition of mesenchymal phenotype through EMT has
been conformed to be associated with aggressive tumor subtypes and poor
clinical outcome in patients. It was observed that cells in
fasting-mimicking medium tended to inhibit HepG2 cell mesenchymal
phenotype. Next, we tracked the movement of HepG2 cells in control
medium or fasting-mimicking medium combined with 20(S)-PPD by the
HoloMonitor M4 time-lapse cytometer. Time-lapse cell-tracking analysis
confirmed that fasted cells showed lower random motility and speed with
20 μM 20(S)-PPD.
Fig. 4.
The motility was anlyzed by real-time holographic imaging.(A) The range
of cell movement was analyzed. And the area and volumn of cells were
also analyzed by HoloMonitorTM M4(B–C). (D) Motility speed of cells were
analyzed. Differences were considered as significant when P < 0.05 (∗) or P < 0.01 (∗∗) or P < 0.001 (∗∗∗).
4. Discussion
Over
the last two decades only 14.1% in 5-year survival rate have been
achieved for patients with HCC, which represents one of the most
aggressive tumors due to its rapid progress. At present, cytotoxic chemotherapy
remains the major treatment option for advanced HCC. Some patients are
allowed to accept targeted therapy, such as sorafinib. However, the
objective response rate (ORR) of sorafenib for advanced HCC is 5% at most.
Moreover, sorafenib still shows adverse effects such as poor
tumor-shrinking effects and relatively high toxicity (e.g., hand-foot
skin reaction).
20(S)-protopanaxadiol (20(S)-PPD), a derivative of ginsenosides, is the final form of protopanaxadiol saponins
metabolized by human intestinal microflora. 20(S)-PPD performs many
biological functions, including differentiation regulation of neural
stem cells and anti-inflammatory properties.
The major novel findings in the present study were that 20(S)-PPD
performed a role in a variety of tumor inhibition. But here's the
question, the effective concentration of 20(S)-PPD is relatively high.
For example, It was reported that 20(S)-PPD inhibited the viability of
HepG2 cell in a dose- and time-dependent manner. But the IC50 values were up to 81.35, 73.5, 48.79 μM at 24, 48 and 72 h, respectively. To enhance the bioavailability of 20(S)-PPD in tumors, novel, safe and effective methods are needed.
According to the cell morphology observed under a microscope, apoptosis, one of the biological processes results in cell death, is observed by a number of typical morphological changes in the structure of the cell (Fig. 2D).
Additionally, data from flow cytometry confirmed that 20(S)-PPD induced
more apoptosis and necrosis in fasting-mimicking medium. Importantly,
fasting-mimicking-alone treatment did not show any significant effects
on proliferation and death of HepG2 cells.
Based on the results of in vitro and in vivo
experiments, our results provided an experimental foundation that
fasting promoted anti-tumor effects of 20(S)-PPD, suggesting that
restrictive dietary interventions might be a potential strategy for
treatments against hepatocellular carcinoma.
These extensively findings
pave the way for future fasting studies in clinical treatment of tumors.
Min kommentar
Vi skulle behöva en motsvarighet till GRETA som drev oponion att världens alla statsledare fick upp ögonen hur j-a (pardon my french) effektiv respektive lands cancerforskning skulle vara om deras cancerforskare fick tillgång till varsitt HoloMonitor instrument.Cancergåtan skulle lösas bra mkt snabbare är jag inte 99% säker på,utan 100% säker.
Ska vi alla phi,are försöka luska reda på en HANS i samma ålder som GRETA så det får max uppmärksamhet? 😎
Mvh the99
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